Pavić, Aleksandar

Link to this page

Authority KeyName Variants
orcid::0000-0003-3233-1341
  • Pavić, Aleksandar (74)
Projects
Microbial diversity study and characterization of beneficial environmental microorganisms Synthesis of new metal complexes and investigation of their reactions with peptides
info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS// The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors
info:eu-repo/grantAgreement/MESTD/inst-2020/200378/RS// Serbian Academy of Sciences and Arts [F128]
SupraMedChem"Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515] Swiss National Science Foundation [PP00P2_170589]
Structure-properties relationships of natural and synthetic molecules and their metal complexes Preclinical investigation of bioactive substances
University of Fribourg European Unions Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie [642095]
Fonds de recherche du Centenaire de l'Universite de Fribourg [818] Chemical and structural designing of nanomaterials for application in medicine and tissue engineering
Bioactive natural products as potential sources of new pharmaceuticals and food supplements Synthesis and characterization of novel functional polymers and polymeric nanocomposites
Characterization and application of fungal metabolites and assessment of new biofungicides potential Graph theory and mathematical programming with applications in chemistry and computer science
Magmatism and geodynamics of the Balkan Peninsula from Mesozoic to present day: significance for the formation of metallic and non-metallic mineral deposits info:eu-repo/grantAgreement/MESTD/inst-2020/200007/RS//
info:eu-repo/grantAgreement/MESTD/inst-2020/200122/RS// info:eu-repo/grantAgreement/MESTD/inst-2020/200125/RS//
Production of new dietetic milk products for risk populations based on qualitative and quantitative analysis of health risk markers in milk consumption Serbian Academy of Sciences and Arts
Serbian Academy of Sciences and Arts [F80] Supra-MedChem'Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515]
SupraMedChem'Balkans.Net SCOPES Institutional Partnership [IZ74Z0_160515] Swiss National Science Foundation [200021_196967]
451-03-9/2021-14/20004 Bavarian Equal Opportunities Sponsorship - Forderung von Frauen in Forschung and Lehre (FFL) - Promoting Equal Opportunities for Women in Research and Teaching

Author's Bibliography

Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems

Pavlović, Radoslav Z.; Finnegan, Tyler J.; Metlushko, Anna; Hansen, Alexandar L.; Waudby, Christopher A.; Wang, Xiuze; Hoefer, Nicole; McComb, David W.; Pavić, Aleksandar; Plackić, Nikola; Novaković, Jovana; Bradić, Jovana; Jeremić, Nevena; Jakovljević, Vladimir; Šmit, Biljana; Matić, Sanja; Alvarez-Saavedra, Matias A.; Čapo, Ivan; Moore, Curtis E.; Stupp, Samuel I.; Badjić, Jovica D.

(2023)

TY  - JOUR
AU  - Pavlović, Radoslav Z.
AU  - Finnegan, Tyler J.
AU  - Metlushko, Anna
AU  - Hansen, Alexandar L.
AU  - Waudby, Christopher A.
AU  - Wang, Xiuze
AU  - Hoefer, Nicole
AU  - McComb, David W.
AU  - Pavić, Aleksandar
AU  - Plackić, Nikola
AU  - Novaković, Jovana
AU  - Bradić, Jovana
AU  - Jeremić, Nevena
AU  - Jakovljević, Vladimir
AU  - Šmit, Biljana
AU  - Matić, Sanja
AU  - Alvarez-Saavedra, Matias A.
AU  - Čapo, Ivan
AU  - Moore, Curtis E.
AU  - Stupp, Samuel I.
AU  - Badjić, Jovica D.
PY  - 2023
UR  - https://onlinelibrary.wiley.com/doi/abs/10.1002/chem.202303374
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2280
AB  - We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.
T2  - Chemistry – A European Journal
T1  - Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems
IS  - 68
SP  - e202303374
VL  - 29
DO  - 10.1002/chem.202303374
ER  - 
@article{
author = "Pavlović, Radoslav Z. and Finnegan, Tyler J. and Metlushko, Anna and Hansen, Alexandar L. and Waudby, Christopher A. and Wang, Xiuze and Hoefer, Nicole and McComb, David W. and Pavić, Aleksandar and Plackić, Nikola and Novaković, Jovana and Bradić, Jovana and Jeremić, Nevena and Jakovljević, Vladimir and Šmit, Biljana and Matić, Sanja and Alvarez-Saavedra, Matias A. and Čapo, Ivan and Moore, Curtis E. and Stupp, Samuel I. and Badjić, Jovica D.",
year = "2023",
abstract = "We describe the preparation, dynamic, assembly characteristics of vase-shaped basket 13− along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of 1H Nuclear Magnetic Resonance (NMR), 1H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with 1 forming dimer [12]6−, to be in equilibrium with monomers 1(R)3− (relaxed) and 1(S)3− (squeezed). Through simultaneous line-shape analysis of 1H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket 1(R)3− includes anticancer drug mitoxantrone (MTO2+) in its pocket to give stable binary complex [MTO⊂1]− (Kd=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well-characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep-cavity baskets.",
journal = "Chemistry – A European Journal",
title = "Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems",
number = "68",
pages = "e202303374",
volume = "29",
doi = "10.1002/chem.202303374"
}
Pavlović, R. Z., Finnegan, T. J., Metlushko, A., Hansen, A. L., Waudby, C. A., Wang, X., Hoefer, N., McComb, D. W., Pavić, A., Plackić, N., Novaković, J., Bradić, J., Jeremić, N., Jakovljević, V., Šmit, B., Matić, S., Alvarez-Saavedra, M. A., Čapo, I., Moore, C. E., Stupp, S. I.,& Badjić, J. D.. (2023). Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems. in Chemistry – A European Journal, 29(68), e202303374.
https://doi.org/10.1002/chem.202303374
Pavlović RZ, Finnegan TJ, Metlushko A, Hansen AL, Waudby CA, Wang X, Hoefer N, McComb DW, Pavić A, Plackić N, Novaković J, Bradić J, Jeremić N, Jakovljević V, Šmit B, Matić S, Alvarez-Saavedra MA, Čapo I, Moore CE, Stupp SI, Badjić JD. Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems. in Chemistry – A European Journal. 2023;29(68):e202303374.
doi:10.1002/chem.202303374 .
Pavlović, Radoslav Z., Finnegan, Tyler J., Metlushko, Anna, Hansen, Alexandar L., Waudby, Christopher A., Wang, Xiuze, Hoefer, Nicole, McComb, David W., Pavić, Aleksandar, Plackić, Nikola, Novaković, Jovana, Bradić, Jovana, Jeremić, Nevena, Jakovljević, Vladimir, Šmit, Biljana, Matić, Sanja, Alvarez-Saavedra, Matias A., Čapo, Ivan, Moore, Curtis E., Stupp, Samuel I., Badjić, Jovica D., "Dynamic and Assembly Characteristics of Deep-Cavity Basket Acting as a Host for Inclusion Complexation of Mitoxantrone in Biotic and Abiotic Systems" in Chemistry – A European Journal, 29, no. 68 (2023):e202303374,
https://doi.org/10.1002/chem.202303374 . .
8

Maqui berry extract inhibits filamentation of Candidaalbicans and improves the antifungal efficacy of nystatin

Joncić Savić, Katarina; Đokic, Lidija; Stanković, Nada; Morić, Ivana; Pavlović, Bojan; Šenerović, Lidija; Aydogan, Cem; Pavić, Aleksandar

(2023)

TY  - JOUR
AU  - Joncić Savić, Katarina
AU  - Đokic, Lidija
AU  - Stanković, Nada
AU  - Morić, Ivana
AU  - Pavlović, Bojan
AU  - Šenerović, Lidija
AU  - Aydogan, Cem
AU  - Pavić, Aleksandar
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S1756464623002177
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1982
AB  - Candidiasis caused by Candida albicans is one of the most common fungal infections in modern society. The limited arsenal of clinical drugs, their side effects and emerging resistance, largely contribute to the low efficacy of current antifungal therapies. The morphogenetic yeast-to-hyphae transition is the key virulence feature for the establishment of local and systemic C. albicans infections. We show that a delfinidin-rich fruit extract from Aristotelia chilensis ([Molina], Stuntz) (maqui berry) inhibits filamentation of C. albicans, in both laboratory and clinical strains. The extract acts synergistically with nystatin, with filament formation completely prevented by the combination of ¼×MIC of nystatin and 0.125 mg/ml of the extract. The combination treatment results in increased survival of C. albicans-infected zebrafish embryos compared to treatment with nystatin. Neither the extract nor its combination with nystatin was toxic at effective doses. These results warrant further investigation of maqui berry extract as adjuvant antifungal treatment.
T2  - Journal of Functional Foods
T1  - Maqui berry extract inhibits filamentation of Candidaalbicans and improves the antifungal efficacy of nystatin
SP  - 105617
VL  - 106
DO  - 10.1016/j.jff.2023.105617
ER  - 
@article{
author = "Joncić Savić, Katarina and Đokic, Lidija and Stanković, Nada and Morić, Ivana and Pavlović, Bojan and Šenerović, Lidija and Aydogan, Cem and Pavić, Aleksandar",
year = "2023",
abstract = "Candidiasis caused by Candida albicans is one of the most common fungal infections in modern society. The limited arsenal of clinical drugs, their side effects and emerging resistance, largely contribute to the low efficacy of current antifungal therapies. The morphogenetic yeast-to-hyphae transition is the key virulence feature for the establishment of local and systemic C. albicans infections. We show that a delfinidin-rich fruit extract from Aristotelia chilensis ([Molina], Stuntz) (maqui berry) inhibits filamentation of C. albicans, in both laboratory and clinical strains. The extract acts synergistically with nystatin, with filament formation completely prevented by the combination of ¼×MIC of nystatin and 0.125 mg/ml of the extract. The combination treatment results in increased survival of C. albicans-infected zebrafish embryos compared to treatment with nystatin. Neither the extract nor its combination with nystatin was toxic at effective doses. These results warrant further investigation of maqui berry extract as adjuvant antifungal treatment.",
journal = "Journal of Functional Foods",
title = "Maqui berry extract inhibits filamentation of Candidaalbicans and improves the antifungal efficacy of nystatin",
pages = "105617",
volume = "106",
doi = "10.1016/j.jff.2023.105617"
}
Joncić Savić, K., Đokic, L., Stanković, N., Morić, I., Pavlović, B., Šenerović, L., Aydogan, C.,& Pavić, A.. (2023). Maqui berry extract inhibits filamentation of Candidaalbicans and improves the antifungal efficacy of nystatin. in Journal of Functional Foods, 106, 105617.
https://doi.org/10.1016/j.jff.2023.105617
Joncić Savić K, Đokic L, Stanković N, Morić I, Pavlović B, Šenerović L, Aydogan C, Pavić A. Maqui berry extract inhibits filamentation of Candidaalbicans and improves the antifungal efficacy of nystatin. in Journal of Functional Foods. 2023;106:105617.
doi:10.1016/j.jff.2023.105617 .
Joncić Savić, Katarina, Đokic, Lidija, Stanković, Nada, Morić, Ivana, Pavlović, Bojan, Šenerović, Lidija, Aydogan, Cem, Pavić, Aleksandar, "Maqui berry extract inhibits filamentation of Candidaalbicans and improves the antifungal efficacy of nystatin" in Journal of Functional Foods, 106 (2023):105617,
https://doi.org/10.1016/j.jff.2023.105617 . .

Three lines of evidence of the hepatotoxicity young researchers of a mixture containing phthalates and bisphenol a: in silico and two in vivo models

Baralić, Katarina; Pavić, Aleksandar; Javorac, Dragana; Živančević, Katarina; Božić, Dragica; Radaković, Nataša; Antonijević Miljaković, Evica; Buha Djordjevic, Aleksandra; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

(Beograd : Udruženje toksikologa Srbije, 2023)

TY  - CONF
AU  - Baralić, Katarina
AU  - Pavić, Aleksandar
AU  - Javorac, Dragana
AU  - Živančević, Katarina
AU  - Božić, Dragica
AU  - Radaković, Nataša
AU  - Antonijević Miljaković, Evica
AU  - Buha Djordjevic, Aleksandra
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2283
AB  - The extensive usage of bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A
(BPA) creates a lot of opportunities for combined human exposure to these hazardous compounds in
everyday life and a variety of negative outcomes, including hepatotoxicity. In silico research and two
in vivo models were used to investigate the links between a mixture including DEHP, DBP and BPA and
liver injury. Bioinformatic analysis was performed by Comparative Toxicogenomics Database, ShinyGO,
ToppCluster, and Cytoscape. In vivo subacute study included five groups of rats (n = 6): (1) Control: corn
oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP
+ DBP + BPA. Zebrafish embryos were exposed to the investigated substances in multiple dosages, both
alone and in combination (binary and ternary mixtures). Liver damage was linked to 75 DEHP, DBP, and
BPA genes, the majority of which were associated with inflammation/oxidative stress, identified as the
most relevant molecular pathways. In rats, significant changes in redox status/bioelements’ level and
pathohistology were more pronounced or evident only in MIX group, suggesting probable additivity.
In a dose-dependent manner, BPA reduced the liver area (LA) index. LA values were decreased by DEHP
(2 μg/mL) and DBP (5 μg/mL), whereas LA index was raised by their higher concentrations. In binary
mixtures, DBP had a lethal effect at the two highest concentrations, whereas BPA directed hepatotoxicity
of the DEHP/DBP/BPA mixture.
PB  - Beograd : Udruženje toksikologa Srbije
C3  - 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities
T1  - Three lines of evidence of the hepatotoxicity young researchers of a mixture containing phthalates and bisphenol a: in silico and two in vivo models
EP  - 56
SP  - 56
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2283
ER  - 
@conference{
author = "Baralić, Katarina and Pavić, Aleksandar and Javorac, Dragana and Živančević, Katarina and Božić, Dragica and Radaković, Nataša and Antonijević Miljaković, Evica and Buha Djordjevic, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "The extensive usage of bis(2-ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP), and bisphenol A
(BPA) creates a lot of opportunities for combined human exposure to these hazardous compounds in
everyday life and a variety of negative outcomes, including hepatotoxicity. In silico research and two
in vivo models were used to investigate the links between a mixture including DEHP, DBP and BPA and
liver injury. Bioinformatic analysis was performed by Comparative Toxicogenomics Database, ShinyGO,
ToppCluster, and Cytoscape. In vivo subacute study included five groups of rats (n = 6): (1) Control: corn
oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP
+ DBP + BPA. Zebrafish embryos were exposed to the investigated substances in multiple dosages, both
alone and in combination (binary and ternary mixtures). Liver damage was linked to 75 DEHP, DBP, and
BPA genes, the majority of which were associated with inflammation/oxidative stress, identified as the
most relevant molecular pathways. In rats, significant changes in redox status/bioelements’ level and
pathohistology were more pronounced or evident only in MIX group, suggesting probable additivity.
In a dose-dependent manner, BPA reduced the liver area (LA) index. LA values were decreased by DEHP
(2 μg/mL) and DBP (5 μg/mL), whereas LA index was raised by their higher concentrations. In binary
mixtures, DBP had a lethal effect at the two highest concentrations, whereas BPA directed hepatotoxicity
of the DEHP/DBP/BPA mixture.",
publisher = "Beograd : Udruženje toksikologa Srbije",
journal = "13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities",
title = "Three lines of evidence of the hepatotoxicity young researchers of a mixture containing phthalates and bisphenol a: in silico and two in vivo models",
pages = "56-56",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2283"
}
Baralić, K., Pavić, A., Javorac, D., Živančević, K., Božić, D., Radaković, N., Antonijević Miljaković, E., Buha Djordjevic, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Three lines of evidence of the hepatotoxicity young researchers of a mixture containing phthalates and bisphenol a: in silico and two in vivo models. in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities
Beograd : Udruženje toksikologa Srbije., 56-56.
https://hdl.handle.net/21.15107/rcub_imagine_2283
Baralić K, Pavić A, Javorac D, Živančević K, Božić D, Radaković N, Antonijević Miljaković E, Buha Djordjevic A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Three lines of evidence of the hepatotoxicity young researchers of a mixture containing phthalates and bisphenol a: in silico and two in vivo models. in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities. 2023;:56-56.
https://hdl.handle.net/21.15107/rcub_imagine_2283 .
Baralić, Katarina, Pavić, Aleksandar, Javorac, Dragana, Živančević, Katarina, Božić, Dragica, Radaković, Nataša, Antonijević Miljaković, Evica, Buha Djordjevic, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Three lines of evidence of the hepatotoxicity young researchers of a mixture containing phthalates and bisphenol a: in silico and two in vivo models" in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities (2023):56-56,
https://hdl.handle.net/21.15107/rcub_imagine_2283 .

Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes

Sovari, Sara Nasiri; Kolly, Isabelle; Schindler, Kevin; Đurić, Ana; Srdić-Rajić, Tatjana; Crochet, Aurelien; Pavić, Aleksandar; Zobi, Fabio

(2023)

TY  - JOUR
AU  - Sovari, Sara Nasiri
AU  - Kolly, Isabelle
AU  - Schindler, Kevin
AU  - Đurić, Ana
AU  - Srdić-Rajić, Tatjana
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Zobi, Fabio
PY  - 2023
UR  - https://pubs.rsc.org/en/content/articlelanding/2023/dt/d2dt04041g
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1981
AB  - We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able to undergo ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2′-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 μM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination.
T2  - Dalton Transactions
T1  - Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes
EP  - 6944
IS  - 20
SP  - 6934
VL  - 52
DO  - 10.1039/D2DT04041G
ER  - 
@article{
author = "Sovari, Sara Nasiri and Kolly, Isabelle and Schindler, Kevin and Đurić, Ana and Srdić-Rajić, Tatjana and Crochet, Aurelien and Pavić, Aleksandar and Zobi, Fabio",
year = "2023",
abstract = "We report the synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. The study was promoted in order to understand if the presence and position of a reactive halomethyl substituent on the diimine ligand system of fac-[Re(CO)3]+ species may be a key molecular feature for the design of active and non-toxic anticancer agents. Only compounds potentially able to undergo ligand-based alkylating reactions show significant antiproliferative activity against colorectal and pancreatic cell lines. Of the new species presented in this study, one compound (5-(chloromethyl)-2,2′-bipyridine derivative) shows significant inhibition of pancreatic tumour growth in vivo in zebrafish-Panc-1 xenografts. The complex is noticeably effective at 8 μM concentration, lower than its in vitro IC50 values, being also capable of inhibiting in vivo cancer cells dissemination.",
journal = "Dalton Transactions",
title = "Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes",
pages = "6944-6934",
number = "20",
volume = "52",
doi = "10.1039/D2DT04041G"
}
Sovari, S. N., Kolly, I., Schindler, K., Đurić, A., Srdić-Rajić, T., Crochet, A., Pavić, A.,& Zobi, F.. (2023). Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. in Dalton Transactions, 52(20), 6934-6944.
https://doi.org/10.1039/D2DT04041G
Sovari SN, Kolly I, Schindler K, Đurić A, Srdić-Rajić T, Crochet A, Pavić A, Zobi F. Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes. in Dalton Transactions. 2023;52(20):6934-6944.
doi:10.1039/D2DT04041G .
Sovari, Sara Nasiri, Kolly, Isabelle, Schindler, Kevin, Đurić, Ana, Srdić-Rajić, Tatjana, Crochet, Aurelien, Pavić, Aleksandar, Zobi, Fabio, "Synthesis, characterization, and in vivo evaluation of the anticancer activity of a series of 5- and 6-(halomethyl)-2,2′-bipyridine rhenium tricarbonyl complexes" in Dalton Transactions, 52, no. 20 (2023):6934-6944,
https://doi.org/10.1039/D2DT04041G . .
3
2

Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study

Ružić, Dušan; Đoković, Nemanja; Santibanez, Juan; Pavić, Aleksandar; Ganesan, A.; Srdić- Rajić, Tatjana; Nikolić, Katarina

(Belgrade : Serbian Association on for Cancer Research, 2023)

TY  - CONF
AU  - Ružić, Dušan
AU  - Đoković, Nemanja
AU  - Santibanez, Juan
AU  - Pavić, Aleksandar
AU  - Ganesan, A.
AU  - Srdić- Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://www.sdir.ac.rs/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2096
AB  - Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the
absence of specifi c molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human
epidermal growth factor receptor 2 (HER2). In the era of precision oncology, it is recognized that an imbalance in posttransla
tional modifi cations of histones, such as histone lysine acetylation and deacetylation, is closely linked to tumor
initiation and progression. Two groups of enzymes control the reversible nature of histone post-translational acetylation:
histone acetyltransferases (HATs) and histone deacetylases (HDACs). Isoform-specifi c targeting of HDACs is considered
a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, nonselec
tive HDAC inhibitors have been more extensively studied in clinical trials. This work presents the design and
discovery of potent HDAC inhibitors that selectively target HDAC6 isozyme, using 1-benzhydryl piperazine as a surface
recognition group with diff erent hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with
nanomolar IC50 values and two non-selective HDAC inhibitors were identifi ed. Structure-based molecular modelling
was utilized to investigate the impact of linker chemistry on the potency of synthesized inhibitors against HDAC6. The
anti-cancer, anti-migratory, and anti-invasive activities of these compounds were evaluated using breast cancer cell
lines (MDA-MB-231 and MCF-7). Experiments on a zebrafi sh MDA-MB-231 xenograft model demonstrated that a novel
non-selective HDAC inhibitor (compound 8b) with a seven-carbon-atom linker exhibited potent eff ects against tumor
growth, metastasis, and angiogenesis at low micromolar concentrations.
PB  - Belgrade :  Serbian Association on for Cancer Research
C3  - 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR)
T1  - Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study
EP  - 26
IS  - 1
SP  - 26
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2096
ER  - 
@conference{
author = "Ružić, Dušan and Đoković, Nemanja and Santibanez, Juan and Pavić, Aleksandar and Ganesan, A. and Srdić- Rajić, Tatjana and Nikolić, Katarina",
year = "2023",
abstract = "Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the
absence of specifi c molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human
epidermal growth factor receptor 2 (HER2). In the era of precision oncology, it is recognized that an imbalance in posttransla
tional modifi cations of histones, such as histone lysine acetylation and deacetylation, is closely linked to tumor
initiation and progression. Two groups of enzymes control the reversible nature of histone post-translational acetylation:
histone acetyltransferases (HATs) and histone deacetylases (HDACs). Isoform-specifi c targeting of HDACs is considered
a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, nonselec
tive HDAC inhibitors have been more extensively studied in clinical trials. This work presents the design and
discovery of potent HDAC inhibitors that selectively target HDAC6 isozyme, using 1-benzhydryl piperazine as a surface
recognition group with diff erent hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with
nanomolar IC50 values and two non-selective HDAC inhibitors were identifi ed. Structure-based molecular modelling
was utilized to investigate the impact of linker chemistry on the potency of synthesized inhibitors against HDAC6. The
anti-cancer, anti-migratory, and anti-invasive activities of these compounds were evaluated using breast cancer cell
lines (MDA-MB-231 and MCF-7). Experiments on a zebrafi sh MDA-MB-231 xenograft model demonstrated that a novel
non-selective HDAC inhibitor (compound 8b) with a seven-carbon-atom linker exhibited potent eff ects against tumor
growth, metastasis, and angiogenesis at low micromolar concentrations.",
publisher = "Belgrade :  Serbian Association on for Cancer Research",
journal = "6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR)",
title = "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study",
pages = "26-26",
number = "1",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2096"
}
Ružić, D., Đoković, N., Santibanez, J., Pavić, A., Ganesan, A., Srdić- Rajić, T.,& Nikolić, K.. (2023). Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study. in 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR)
Belgrade :  Serbian Association on for Cancer Research.(1), 26-26.
https://hdl.handle.net/21.15107/rcub_imagine_2096
Ružić D, Đoković N, Santibanez J, Pavić A, Ganesan A, Srdić- Rajić T, Nikolić K. Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study. in 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR). 2023;(1):26-26.
https://hdl.handle.net/21.15107/rcub_imagine_2096 .
Ružić, Dušan, Đoković, Nemanja, Santibanez, Juan, Pavić, Aleksandar, Ganesan, A., Srdić- Rajić, Tatjana, Nikolić, Katarina, "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study" in 6th Congress of the Serbian AssociaƟ on for Cancer Research (SDIR), no. 1 (2023):26-26,
https://hdl.handle.net/21.15107/rcub_imagine_2096 .

Sulforaphane affects morphological changes and cell viability of colon cancer cells: p53 mutation-dependent effect

Đurić, Ana; Srdić-Rajić, Tatjana; Božić, Dragica; Baralić, Katarina; Pavić, Aleksandar; Đukić-Ćosić, Danijela

(Beograd : Udruženje toksikologa Srbije, 2023)

TY  - CONF
AU  - Đurić, Ana
AU  - Srdić-Rajić, Tatjana
AU  - Božić, Dragica
AU  - Baralić, Katarina
AU  - Pavić, Aleksandar
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2284
AB  - Colorectal carcinoma (CRC) is an increasing cause of morbidity and mortality worldwide.
Among biologically active compounds which have been shown to exert cytotoxic effects on human cancer
cells, including CRC, is sulforaphane (SFN), an isothiocyanate compound extracted from cruciferous
vegetables, especially broccoli. This in vitro study aimed to investigate the effect of SFN on the growth
of human CRC cells and its dependency on the expression of p53. Two human CRC cell lines: HT-29
(a p53 mutated line) and HT-116 (a p53 wild-type line) were treated with SFN at concentrations of 0, 4,
8, 16, and 32 μmol/L for 72 h to test its anticancer effect.
Results indicated that SFN induced cell morphological changes and decreased the total number
of viable cells. Treatment of CRC cells with SFN for 72 h resulted in moderate dose-dependent cytotoxicity.
HCT-116 cells, with a p53-wt, were more sensitive (IC50 = 8.41 μM) than p53-mutated HT-29 cells (IC50
= 24.83 μM). These results indicate that SFN exhibits the anticancer effect against CRC cells in p53 mutation-
dependent manner (Serbia-China project: 451-03-1203/2021-09).
PB  - Beograd : Udruženje toksikologa Srbije
C3  - 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities
T1  - Sulforaphane affects morphological changes and cell viability of colon cancer cells: p53 mutation-dependent effect
EP  - 180
SP  - 180
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2284
ER  - 
@conference{
author = "Đurić, Ana and Srdić-Rajić, Tatjana and Božić, Dragica and Baralić, Katarina and Pavić, Aleksandar and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Colorectal carcinoma (CRC) is an increasing cause of morbidity and mortality worldwide.
Among biologically active compounds which have been shown to exert cytotoxic effects on human cancer
cells, including CRC, is sulforaphane (SFN), an isothiocyanate compound extracted from cruciferous
vegetables, especially broccoli. This in vitro study aimed to investigate the effect of SFN on the growth
of human CRC cells and its dependency on the expression of p53. Two human CRC cell lines: HT-29
(a p53 mutated line) and HT-116 (a p53 wild-type line) were treated with SFN at concentrations of 0, 4,
8, 16, and 32 μmol/L for 72 h to test its anticancer effect.
Results indicated that SFN induced cell morphological changes and decreased the total number
of viable cells. Treatment of CRC cells with SFN for 72 h resulted in moderate dose-dependent cytotoxicity.
HCT-116 cells, with a p53-wt, were more sensitive (IC50 = 8.41 μM) than p53-mutated HT-29 cells (IC50
= 24.83 μM). These results indicate that SFN exhibits the anticancer effect against CRC cells in p53 mutation-
dependent manner (Serbia-China project: 451-03-1203/2021-09).",
publisher = "Beograd : Udruženje toksikologa Srbije",
journal = "13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities",
title = "Sulforaphane affects morphological changes and cell viability of colon cancer cells: p53 mutation-dependent effect",
pages = "180-180",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2284"
}
Đurić, A., Srdić-Rajić, T., Božić, D., Baralić, K., Pavić, A.,& Đukić-Ćosić, D.. (2023). Sulforaphane affects morphological changes and cell viability of colon cancer cells: p53 mutation-dependent effect. in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities
Beograd : Udruženje toksikologa Srbije., 180-180.
https://hdl.handle.net/21.15107/rcub_imagine_2284
Đurić A, Srdić-Rajić T, Božić D, Baralić K, Pavić A, Đukić-Ćosić D. Sulforaphane affects morphological changes and cell viability of colon cancer cells: p53 mutation-dependent effect. in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities. 2023;:180-180.
https://hdl.handle.net/21.15107/rcub_imagine_2284 .
Đurić, Ana, Srdić-Rajić, Tatjana, Božić, Dragica, Baralić, Katarina, Pavić, Aleksandar, Đukić-Ćosić, Danijela, "Sulforaphane affects morphological changes and cell viability of colon cancer cells: p53 mutation-dependent effect" in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities (2023):180-180,
https://hdl.handle.net/21.15107/rcub_imagine_2284 .

Toxicity testing of D, L-sulforaphane in a zebrafish model

Pavić, Aleksandar; Radaković, Nataša; Srdić-Rajić, Tatjana; Božić, Dragica; Baralić, Katarina; Đukić-Ćosić, Danijela

(Beograd : Udruženje toksikologa Srbije, 2023)

TY  - CONF
AU  - Pavić, Aleksandar
AU  - Radaković, Nataša
AU  - Srdić-Rajić, Tatjana
AU  - Božić, Dragica
AU  - Baralić, Katarina
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2282
AB  - Sulforaphane (SFN) belongs to the group of isothiocyanates and is present in many cruciferous plants,
especially broccoli. The positive properties of this bioactive molecule in the form of extracts have been
shown in numerous studies and include antibacterial, cardioprotective, and neuroprotective effects,
antioxidant and immunomodulatory effects, as well as positive effects in various cancers.
However, the potential for harmful effects of SFN has not been sufficiently investigated, particularly for
chemically obtained D,L-sulforaphane. This study aimed to investigate the toxicity of D,L-sulforaphane
on zebrafish (Danio rerio) model. Wild (AB) strain embryos and zebrafish transgenic lines with fluorescently
labeled liver cells (Tg(fabp:EGFP)) and endothelial cells of blood vessels (Tg(fli1:EGFP)) were used,
treated with different concentrations of SFN (1 to 20 μg/mL).
The survival of embryos, developmental toxicity, hepatotoxicity and cardiotoxicity were monitored for
five days. A concentration of 20 μg/mL of D,L-sulforaphane caused the death of all embryos, while the
median lethal concentration (LC50) was found to be 14.2 μg/mL. D,L-sulforaphane exhibited toxic
effects at concentrations higher than 3 μg/mL, primarily on the development of the swim bladder (4
μg/mL), and growth and development of embryos (4.58 μg/mL), while harmful effects on the liver (liver
size and yolk resorption) were observed at a concentration of 10 μg/mL. Effects on the cardiovascular
system were not observed at concentrations from 1 to 10 μg/mL. The investigation of D,L-sulforaphane
on zebrafish embryos showed that harmful effects occur at very low concentrations, indicating the
need for further investigation of toxicological potential of this molecule.
PB  - Beograd : Udruženje toksikologa Srbije
C3  - 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities
T1  - Toxicity testing of D, L-sulforaphane in a zebrafish model
EP  - 254
SP  - 254
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2282
ER  - 
@conference{
author = "Pavić, Aleksandar and Radaković, Nataša and Srdić-Rajić, Tatjana and Božić, Dragica and Baralić, Katarina and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Sulforaphane (SFN) belongs to the group of isothiocyanates and is present in many cruciferous plants,
especially broccoli. The positive properties of this bioactive molecule in the form of extracts have been
shown in numerous studies and include antibacterial, cardioprotective, and neuroprotective effects,
antioxidant and immunomodulatory effects, as well as positive effects in various cancers.
However, the potential for harmful effects of SFN has not been sufficiently investigated, particularly for
chemically obtained D,L-sulforaphane. This study aimed to investigate the toxicity of D,L-sulforaphane
on zebrafish (Danio rerio) model. Wild (AB) strain embryos and zebrafish transgenic lines with fluorescently
labeled liver cells (Tg(fabp:EGFP)) and endothelial cells of blood vessels (Tg(fli1:EGFP)) were used,
treated with different concentrations of SFN (1 to 20 μg/mL).
The survival of embryos, developmental toxicity, hepatotoxicity and cardiotoxicity were monitored for
five days. A concentration of 20 μg/mL of D,L-sulforaphane caused the death of all embryos, while the
median lethal concentration (LC50) was found to be 14.2 μg/mL. D,L-sulforaphane exhibited toxic
effects at concentrations higher than 3 μg/mL, primarily on the development of the swim bladder (4
μg/mL), and growth and development of embryos (4.58 μg/mL), while harmful effects on the liver (liver
size and yolk resorption) were observed at a concentration of 10 μg/mL. Effects on the cardiovascular
system were not observed at concentrations from 1 to 10 μg/mL. The investigation of D,L-sulforaphane
on zebrafish embryos showed that harmful effects occur at very low concentrations, indicating the
need for further investigation of toxicological potential of this molecule.",
publisher = "Beograd : Udruženje toksikologa Srbije",
journal = "13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities",
title = "Toxicity testing of D, L-sulforaphane in a zebrafish model",
pages = "254-254",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2282"
}
Pavić, A., Radaković, N., Srdić-Rajić, T., Božić, D., Baralić, K.,& Đukić-Ćosić, D.. (2023). Toxicity testing of D, L-sulforaphane in a zebrafish model. in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities
Beograd : Udruženje toksikologa Srbije., 254-254.
https://hdl.handle.net/21.15107/rcub_imagine_2282
Pavić A, Radaković N, Srdić-Rajić T, Božić D, Baralić K, Đukić-Ćosić D. Toxicity testing of D, L-sulforaphane in a zebrafish model. in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities. 2023;:254-254.
https://hdl.handle.net/21.15107/rcub_imagine_2282 .
Pavić, Aleksandar, Radaković, Nataša, Srdić-Rajić, Tatjana, Božić, Dragica, Baralić, Katarina, Đukić-Ćosić, Danijela, "Toxicity testing of D, L-sulforaphane in a zebrafish model" in 13th International congress of the Serbian society of toxicology and 1. TOXSEE regional conference – present and future of toxicology: challenges and opportunities (2023):254-254,
https://hdl.handle.net/21.15107/rcub_imagine_2282 .

Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut

Jonić, Natalija; Chatzigiannis, Christos M.; Koprivica, Ivan; Marinho, Sérgio; Moura-Alves, Pedro; Pavić, Aleksandar; Otašević, Vesna; Pejnović, Nada; Tzakos, Andreas; Stojanović, Ivana

(Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade, 2023)

TY  - CONF
AU  - Jonić, Natalija
AU  - Chatzigiannis, Christos M.
AU  - Koprivica, Ivan
AU  - Marinho, Sérgio
AU  - Moura-Alves, Pedro
AU  - Pavić, Aleksandar
AU  - Otašević, Vesna
AU  - Pejnović, Nada
AU  - Tzakos, Andreas
AU  - Stojanović, Ivana
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2112
AB  - Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T reg- ulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for mod- ulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry. Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice.
Conclusion: C43 can modulate the immune response through the intestine by promoting the im- munosuppressive Treg population.
PB  - Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade
C3  - CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
T1  - Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut
EP  - 38
SP  - 38
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2112
ER  - 
@conference{
author = "Jonić, Natalija and Chatzigiannis, Christos M. and Koprivica, Ivan and Marinho, Sérgio and Moura-Alves, Pedro and Pavić, Aleksandar and Otašević, Vesna and Pejnović, Nada and Tzakos, Andreas and Stojanović, Ivana",
year = "2023",
abstract = "Introduction: The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor which is highly expressed in mucosal tissues - by epithelial cells and immune cells such as Th17 CD4+ and T reg- ulatory cells (Treg). Besides its function of clearing environmental pollutants from the body, it was also revealed that AhR has immunoregulatory effects, thus becoming a potential therapeutic target for mod- ulating the immune response. For that purpose we tested a novel synthetic AhR modulator under the code name C43.
Methods: CYP1A1 (downstream effector of AhR) activation was tested by the EROD assay. Sort-purified CD4+ cells from mesenteric lymph nodes (MLN) were treated with C43 for 24 h. Zebrafish embryos were used to test the toxicity of C43. Male C57BL/6 mice orally received C43 (10 mg/kg) for 5 consecutive days, after which MLN were harvested. Phenotype and function of the cells were analyzed by flow cytometry. Results: C43 showed mild AhR agonistic activity. After treating the sort-purified CD4+ cells with C43, there was a shift in the Th17/Treg ratio in favour of the latter. C43 showed no signs of toxicity when tested on zebrafish embryos. MLN cells from mice that received C43 revealed a shift in the Th1/Treg ratio in favour of Tregs, with a documented rise of the portion of Tregs that expressed CYP1A1 in comparison with the control group of mice.
Conclusion: C43 can modulate the immune response through the intestine by promoting the im- munosuppressive Treg population.",
publisher = "Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade",
journal = "CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia",
title = "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut",
pages = "38-38",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2112"
}
Jonić, N., Chatzigiannis, C. M., Koprivica, I., Marinho, S., Moura-Alves, P., Pavić, A., Otašević, V., Pejnović, N., Tzakos, A.,& Stojanović, I.. (2023). Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia
Institute of Molecular Genetics and Genetic Engineering (IMGGE), University of Belgrade., 38-38.
https://hdl.handle.net/21.15107/rcub_imagine_2112
Jonić N, Chatzigiannis CM, Koprivica I, Marinho S, Moura-Alves P, Pavić A, Otašević V, Pejnović N, Tzakos A, Stojanović I. Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut. in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia. 2023;:38-38.
https://hdl.handle.net/21.15107/rcub_imagine_2112 .
Jonić, Natalija, Chatzigiannis, Christos M., Koprivica, Ivan, Marinho, Sérgio, Moura-Alves, Pedro, Pavić, Aleksandar, Otašević, Vesna, Pejnović, Nada, Tzakos, Andreas, Stojanović, Ivana, "Novel aryl hydrocarbon receptor modulator promotes immunosupressive immune response by stimulating T regulatory cells in the gut" in CoMBoS2 – the Second Congress of Molecular Biologists of Serbia, Abstract Book – Trends in Molecular Biology, Special issue 06-08 October 2023, Belgrade, Serbia (2023):38-38,
https://hdl.handle.net/21.15107/rcub_imagine_2112 .

Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma

Grahovac, J.; Živić, K.; Pavlović, M.; Ostojić, M.; Đurić, A.; Srdić Rajić, T.; Pavić, Aleksandar; Galun, D.

(Wiley, 2023)

TY  - CONF
AU  - Grahovac, J.
AU  - Živić, K.
AU  - Pavlović, M.
AU  - Ostojić, M.
AU  - Đurić, A.
AU  - Srdić Rajić, T.
AU  - Pavić, Aleksandar
AU  - Galun, D.
PY  - 2023
UR  - https://febs.onlinelibrary.wiley.com/doi/10.1002/1878-0261.13471
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1912
AB  - Introduction: Pancreatic ductal adenocarcinoma (PDAC) has dismal
prognosis, as there are no screening tests available, most
often is diagnosed in the metastatic phase of the disease
and is refractory to conventional, targeted and
immunotherapy. We have examined the expression and
role of the novel tumor suppressor nischarin (NISCH) in
PDAC and the effects of treatment with the agonist
rilmenidine (approved for treatment of hypertension) in
order to determine the potential of nischarin agonists for
repurposing in this deadly disease.
PB  - Wiley
C3  - Molecular oncology
T1  - Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma
EP  - 348
IS  - Supplement 1
SP  - 347
VL  - 17
DO  - doi.org/10.1002/1878-0261.13471
ER  - 
@conference{
author = "Grahovac, J. and Živić, K. and Pavlović, M. and Ostojić, M. and Đurić, A. and Srdić Rajić, T. and Pavić, Aleksandar and Galun, D.",
year = "2023",
abstract = "Introduction: Pancreatic ductal adenocarcinoma (PDAC) has dismal
prognosis, as there are no screening tests available, most
often is diagnosed in the metastatic phase of the disease
and is refractory to conventional, targeted and
immunotherapy. We have examined the expression and
role of the novel tumor suppressor nischarin (NISCH) in
PDAC and the effects of treatment with the agonist
rilmenidine (approved for treatment of hypertension) in
order to determine the potential of nischarin agonists for
repurposing in this deadly disease.",
publisher = "Wiley",
journal = "Molecular oncology",
title = "Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma",
pages = "348-347",
number = "Supplement 1",
volume = "17",
doi = "doi.org/10.1002/1878-0261.13471"
}
Grahovac, J., Živić, K., Pavlović, M., Ostojić, M., Đurić, A., Srdić Rajić, T., Pavić, A.,& Galun, D.. (2023). Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma. in Molecular oncology
Wiley., 17(Supplement 1), 347-348.
https://doi.org/doi.org/10.1002/1878-0261.13471
Grahovac J, Živić K, Pavlović M, Ostojić M, Đurić A, Srdić Rajić T, Pavić A, Galun D. Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma. in Molecular oncology. 2023;17(Supplement 1):347-348.
doi:doi.org/10.1002/1878-0261.13471 .
Grahovac, J., Živić, K., Pavlović, M., Ostojić, M., Đurić, A., Srdić Rajić, T., Pavić, Aleksandar, Galun, D., "Preclinical validation of rilmenidine for repurposing in pancreatic ductal adenocarcinoma" in Molecular oncology, 17, no. Supplement 1 (2023):347-348,
https://doi.org/doi.org/10.1002/1878-0261.13471 . .

Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A

Baralić, Katarina; Pavić, Aleksandar; Javorac, Dragana; Živančević, Katarina; Božić, Dragica; Radaković, Nataša; Antonijević Miljaković, Evica; Buha Djordjevic, Aleksandra; Ćurčić, Marijana; Bulat, Zorica; Antonijević, Biljana; Đukić-Ćosić, Danijela

(2023)

TY  - JOUR
AU  - Baralić, Katarina
AU  - Pavić, Aleksandar
AU  - Javorac, Dragana
AU  - Živančević, Katarina
AU  - Božić, Dragica
AU  - Radaković, Nataša
AU  - Antonijević Miljaković, Evica
AU  - Buha Djordjevic, Aleksandra
AU  - Ćurčić, Marijana
AU  - Bulat, Zorica
AU  - Antonijević, Biljana
AU  - Đukić-Ćosić, Danijela
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1661
AB  - Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).
T2  - Journal of Hazardous Materials
T2  - Journal of Hazardous Materials Journal of Hazardous Materials
T1  - Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A
SP  - 130404
VL  - 445
DO  - 10.1016/j.jhazmat.2022.130404
ER  - 
@article{
author = "Baralić, Katarina and Pavić, Aleksandar and Javorac, Dragana and Živančević, Katarina and Božić, Dragica and Radaković, Nataša and Antonijević Miljaković, Evica and Buha Djordjevic, Aleksandra and Ćurčić, Marijana and Bulat, Zorica and Antonijević, Biljana and Đukić-Ćosić, Danijela",
year = "2023",
abstract = "Connections between the mixture containing bis(2- ethylhexyl) phthalate (DEHP), dibutyl phthalate (DBP) and bisphenol A (BPA) and liver injury were explored through in silico investigation and 2 in vivo models. Comparative Toxicogenomics Database (CTD), ShinyGO, ToppCluster and Cytoscape were used for bioinformatic analysis. In vivo subacute study was performed on rats - five groups (n = 6): (1) Control: corn oil, (2) DEHP: 50 mg/kg b.w./day, (3) DBP: 50 mg/kg b.w./day, (4) BPA: 25 mg/kg b.w./day, (5) MIX: DEHP + DBP + BPA. Zebrafish embryos were exposed to the investigated substances in different doses, singularly and combined (binary and ternary mixtures). Liver injury was linked to 75 DEHP, DBP, and BPA genes, mostly connected to inflammation/oxidative stress. In rats, significant alterations in redox status/bioelements and pathohistology were most notable or exclusively present in MIX (probable additive effects). BPA decreased liver area (LA) index in dose-dependent manner. DEHP (< 2 µg/mL) and DBP (≤ 5 µg/mL) reduced LA values, while their higher doses increased LA index. The effect of DBP in binary mixtures led to a lethal outcome at the two highest concentrations, while the hepatotoxicity of DEHP/DBP/BPA mixture was dictated by BPA (confirmed by the benchmark dose analysis).",
journal = "Journal of Hazardous Materials, Journal of Hazardous Materials Journal of Hazardous Materials",
title = "Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A",
pages = "130404",
volume = "445",
doi = "10.1016/j.jhazmat.2022.130404"
}
Baralić, K., Pavić, A., Javorac, D., Živančević, K., Božić, D., Radaković, N., Antonijević Miljaković, E., Buha Djordjevic, A., Ćurčić, M., Bulat, Z., Antonijević, B.,& Đukić-Ćosić, D.. (2023). Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A. in Journal of Hazardous Materials, 445, 130404.
https://doi.org/10.1016/j.jhazmat.2022.130404
Baralić K, Pavić A, Javorac D, Živančević K, Božić D, Radaković N, Antonijević Miljaković E, Buha Djordjevic A, Ćurčić M, Bulat Z, Antonijević B, Đukić-Ćosić D. Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A. in Journal of Hazardous Materials. 2023;445:130404.
doi:10.1016/j.jhazmat.2022.130404 .
Baralić, Katarina, Pavić, Aleksandar, Javorac, Dragana, Živančević, Katarina, Božić, Dragica, Radaković, Nataša, Antonijević Miljaković, Evica, Buha Djordjevic, Aleksandra, Ćurčić, Marijana, Bulat, Zorica, Antonijević, Biljana, Đukić-Ćosić, Danijela, "Comprehensive investigation of hepatotoxicity of the mixture containing phthalates and bisphenol A" in Journal of Hazardous Materials, 445 (2023):130404,
https://doi.org/10.1016/j.jhazmat.2022.130404 . .
1
6
5

Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation

Ruzic, Dusan; Ellinger, Bernhard; Djokovic, Nemanja; Santibanez, Juan F.; Gul, Sheraz; Beljkas, Milan; Djuric, Ana; Ganesan, Arasu; Pavić, Aleksandar; Srdic-Rajic, Tatjana; Petkovic, Milos; Nikolic, Katarina

(2022)

TY  - JOUR
AU  - Ruzic, Dusan
AU  - Ellinger, Bernhard
AU  - Djokovic, Nemanja
AU  - Santibanez, Juan F.
AU  - Gul, Sheraz
AU  - Beljkas, Milan
AU  - Djuric, Ana
AU  - Ganesan, Arasu
AU  - Pavić, Aleksandar
AU  - Srdic-Rajic, Tatjana
AU  - Petkovic, Milos
AU  - Nikolic, Katarina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1662
AB  - Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.
T2  - Pharmaceutics
T2  - Pharmaceutics
T1  - Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation
IS  - 12
SP  - 2600
VL  - 14
DO  - 10.3390/pharmaceutics14122600
ER  - 
@article{
author = "Ruzic, Dusan and Ellinger, Bernhard and Djokovic, Nemanja and Santibanez, Juan F. and Gul, Sheraz and Beljkas, Milan and Djuric, Ana and Ganesan, Arasu and Pavić, Aleksandar and Srdic-Rajic, Tatjana and Petkovic, Milos and Nikolic, Katarina",
year = "2022",
abstract = "Isoform-selective histone deacetylase (HDAC) inhibition is promoted as a rational strategy to develop safer anti-cancer drugs compared to non-selective HDAC inhibitors. Despite this presumed benefit, considerably more non-selective HDAC inhibitors have undergone clinical trials. In this report, we detail the design and discovery of potent HDAC inhibitors, with 1-benzhydryl piperazine as a surface recognition group, that differ in hydrocarbon linker. In vitro HDAC screening identified two selective HDAC6 inhibitors with nanomolar IC50 values, as well as two non-selective nanomolar HDAC inhibitors. Structure-based molecular modeling was employed to study the influence of linker chemistry of synthesized inhibitors on HDAC6 potency. The breast cancer cell lines (MDA-MB-231 and MCF-7) were used to evaluate compound-mediated in vitro anti-cancer, anti-migratory, and anti-invasive activities. Experiments on the zebrafish MDA-MB-231 xenograft model revealed that a novel non-selective HDAC inhibitor with a seven-carbon-atom linker exhibits potent anti-tumor, anti-metastatic, and anti-angiogenic effects when tested at low micromolar concentrations.",
journal = "Pharmaceutics, Pharmaceutics",
title = "Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation",
number = "12",
pages = "2600",
volume = "14",
doi = "10.3390/pharmaceutics14122600"
}
Ruzic, D., Ellinger, B., Djokovic, N., Santibanez, J. F., Gul, S., Beljkas, M., Djuric, A., Ganesan, A., Pavić, A., Srdic-Rajic, T., Petkovic, M.,& Nikolic, K.. (2022). Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation. in Pharmaceutics, 14(12), 2600.
https://doi.org/10.3390/pharmaceutics14122600
Ruzic D, Ellinger B, Djokovic N, Santibanez JF, Gul S, Beljkas M, Djuric A, Ganesan A, Pavić A, Srdic-Rajic T, Petkovic M, Nikolic K. Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation. in Pharmaceutics. 2022;14(12):2600.
doi:10.3390/pharmaceutics14122600 .
Ruzic, Dusan, Ellinger, Bernhard, Djokovic, Nemanja, Santibanez, Juan F., Gul, Sheraz, Beljkas, Milan, Djuric, Ana, Ganesan, Arasu, Pavić, Aleksandar, Srdic-Rajic, Tatjana, Petkovic, Milos, Nikolic, Katarina, "Discovery of 1-Benzhydryl-Piperazine-Based HDAC Inhibitors with Anti-Breast Cancer Activity: Synthesis, Molecular Modeling, In Vitro and In Vivo Biological Evaluation" in Pharmaceutics, 14, no. 12 (2022):2600,
https://doi.org/10.3390/pharmaceutics14122600 . .
3
9
7

Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells

Krstić, Aleksandra; Pavić, Aleksandar; Balint, Vanda; Lazić, Stefan; Avdović, Edina; Marković, Zoran; Pejić, Jelena; Stevanović, Milena; Petrović, Isidora

(2022)

TY  - CONF
AU  - Krstić, Aleksandra
AU  - Pavić, Aleksandar
AU  - Balint, Vanda
AU  - Lazić, Stefan
AU  - Avdović, Edina
AU  - Marković, Zoran
AU  - Pejić, Jelena
AU  - Stevanović, Milena
AU  - Petrović, Isidora
PY  - 2022
UR  - https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1866
AB  - Pancreatic carcinoma represents one of the most lethal malignant diseases in the world although some
progress has been made in treating the disease in the past decades. Current multi-agent treatment options
have improved the overall survival of patients, but more effective treatment strategies are still needed. In this
paper we have characterized anticancer potential of coumarin-palladium(II) complex against pancreatic
carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were
assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented
results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being
effective at micromolar concentrations (0.5 M). Treatments induced apoptosis, increased BAX/BCL-2 ratio
and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in
pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma
xenografts resulted in significant reduction of tumor mass, while did not provoke any adverse toxic effects
including hepatotoxicity. Presented results indicate the great potential of tested compound and the
perspective of its further development towards pancreatic cancer therapy.
C3  - RAD International concerence on radiation in various fields of research
T1  - Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells
IS  - Spring Edition
SP  - 34
DO  - 10.21175/rad.spr.abstr.book.2022.9.3
ER  - 
@conference{
author = "Krstić, Aleksandra and Pavić, Aleksandar and Balint, Vanda and Lazić, Stefan and Avdović, Edina and Marković, Zoran and Pejić, Jelena and Stevanović, Milena and Petrović, Isidora",
year = "2022",
abstract = "Pancreatic carcinoma represents one of the most lethal malignant diseases in the world although some
progress has been made in treating the disease in the past decades. Current multi-agent treatment options
have improved the overall survival of patients, but more effective treatment strategies are still needed. In this
paper we have characterized anticancer potential of coumarin-palladium(II) complex against pancreatic
carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were
assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented
results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being
effective at micromolar concentrations (0.5 M). Treatments induced apoptosis, increased BAX/BCL-2 ratio
and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in
pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma
xenografts resulted in significant reduction of tumor mass, while did not provoke any adverse toxic effects
including hepatotoxicity. Presented results indicate the great potential of tested compound and the
perspective of its further development towards pancreatic cancer therapy.",
journal = "RAD International concerence on radiation in various fields of research",
title = "Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells",
number = "Spring Edition",
pages = "34",
doi = "10.21175/rad.spr.abstr.book.2022.9.3"
}
Krstić, A., Pavić, A., Balint, V., Lazić, S., Avdović, E., Marković, Z., Pejić, J., Stevanović, M.,& Petrović, I.. (2022). Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells. in RAD International concerence on radiation in various fields of research(Spring Edition), 34.
https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3
Krstić A, Pavić A, Balint V, Lazić S, Avdović E, Marković Z, Pejić J, Stevanović M, Petrović I. Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells. in RAD International concerence on radiation in various fields of research. 2022;(Spring Edition):34.
doi:10.21175/rad.spr.abstr.book.2022.9.3 .
Krstić, Aleksandra, Pavić, Aleksandar, Balint, Vanda, Lazić, Stefan, Avdović, Edina, Marković, Zoran, Pejić, Jelena, Stevanović, Milena, Petrović, Isidora, "Coumarin-palladium(II) complex acts as a potent and nontoxic anticancer agent against pancreatic carcinoma cells" in RAD International concerence on radiation in various fields of research, no. Spring Edition (2022):34,
https://doi.org/10.21175/rad.spr.abstr.book.2022.9.3 . .

Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo

Hertrampf, Gesa; Kusserow, Kalina; Vojnović, Sandra; Pavić, Aleksandar; Mueller, Jonas, I; Nikodinović-Runić, Jasmina; Gulder, Tobias A. M.

(Wiley-V C H Verlag Gmbh, Weinheim, 2022)

TY  - JOUR
AU  - Hertrampf, Gesa
AU  - Kusserow, Kalina
AU  - Vojnović, Sandra
AU  - Pavić, Aleksandar
AU  - Mueller, Jonas, I
AU  - Nikodinović-Runić, Jasmina
AU  - Gulder, Tobias A. M.
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1553
AB  - The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Chemistry-A European Journal
T1  - Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo
IS  - 32
VL  - 28
DO  - 10.1002/chem.202200394
ER  - 
@article{
author = "Hertrampf, Gesa and Kusserow, Kalina and Vojnović, Sandra and Pavić, Aleksandar and Mueller, Jonas, I and Nikodinović-Runić, Jasmina and Gulder, Tobias A. M.",
year = "2022",
abstract = "The increasing emergence of resistances against established antibiotics is a substantial threat to human health. The discovery of new compounds with potent antibiotic activity is thus of utmost importance. Within this work, we identify strong antibiotic activity of the natural product myxocoumarin B from Stigmatella aurantiaca MYX-030 against a range of clinically relevant bacterial pathogens, including clinical isolates of MRSA. A focused library of structural analogs was synthesized to explore initial structure-activity relationships and to identify equipotent myxocoumarin derivatives devoid of the natural nitro substituent to significantly streamline synthetic access. The cytotoxicity of the myxocoumarins as well as their potential to cure bacterial infections in vivo was established using a zebrafish model system. Our results reveal the exceptional antibiotic activity of the myxocoumarin scaffold and hence its potential for the development of novel antibiotics.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Chemistry-A European Journal",
title = "Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo",
number = "32",
volume = "28",
doi = "10.1002/chem.202200394"
}
Hertrampf, G., Kusserow, K., Vojnović, S., Pavić, A., Mueller, J. I., Nikodinović-Runić, J.,& Gulder, T. A. M.. (2022). Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo. in Chemistry-A European Journal
Wiley-V C H Verlag Gmbh, Weinheim., 28(32).
https://doi.org/10.1002/chem.202200394
Hertrampf G, Kusserow K, Vojnović S, Pavić A, Mueller JI, Nikodinović-Runić J, Gulder TAM. Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo. in Chemistry-A European Journal. 2022;28(32).
doi:10.1002/chem.202200394 .
Hertrampf, Gesa, Kusserow, Kalina, Vojnović, Sandra, Pavić, Aleksandar, Mueller, Jonas, I, Nikodinović-Runić, Jasmina, Gulder, Tobias A. M., "Strong Antibiotic Activity of the Myxocoumarin Scaffold in vitro and in vivo" in Chemistry-A European Journal, 28, no. 32 (2022),
https://doi.org/10.1002/chem.202200394 . .
9
1
1

Novi pristupi u tretmanu hroničnih bakterijskih i gljivičnih infekcija

Pavić, Aleksandar

(Beograd : Srpsko biološko društvo, 2022)

TY  - CONF
AU  - Pavić, Aleksandar
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1745
AB  - Hronične infekcije izazvane bakterijama i gljivama predstavljaju rastući
globalni zdravstveni problem, posebno u svetlu svakodnevnog povećanja broja
imunokompromitovanih osoba (HIV, dijabetes), onkoloških pacijenata,
autoimunskih oboljenja (cistična fibroza, bronhiektaze), i pacijenata na
kortikosterioidnoj terapiji ili sa transplantacijom organa. Ovakve infekcije
su po svojoj prirodi najčešće polimikrobne i karakterišu se prisustvom
različitih vrsta bakterija ili bakterija i gljiva, koji koegzistiraju u vidu
visoko uređenih zajednica poznatih kao biofilm.1 Hronične infekcije se čak u
više od 80% slučajeva karakterišu postojanjem biofilmova, unutar kojih su
ćelije patogenih mikroorganizama zaštićene od dejstva antimikrobnih
terapeutika i imunskog sistema, dok im je virulentnost dosta povećana, što
značajno umanjuje efikasnost lečenja konvencionalnim antimikrobnim lekovima.
Dodatni izazov u kliničkoj praksi predstavljaju širenje antimikrobne
rezistencije i ograničen broj klasa antimikrobnih lekova, kao i stagnacija
farmaceutske industrije u razvoju inovativnih antibiotika sa drugačijim
mehanizmom delovanja, a posebno antimikotika.1,2 Stoga, kontrola formiranja
biofilma kao rezervoara infektivnih agenasa, i ekspresije faktora virulencije
patogena koji vode ka narušavanju integriteta inficiranih tkiva domaćina
predstavljaju jedan od ključnih koraka za efikasan tretman hroničnih infekcija.
Dodatno, primena inhibitora međućelijske komunikacije, terapija
bakteriofagima, jačanje odbrambenog kapaciteta imunskog sistema, kao i
manipulacija celokupnim mikrobiomom predstavljaju samo neke od najnovijih
pristupa u lečenju hroničnih infekcija
AB  - Хроничне инфекције изазване бактеријама и гљивама представљају растући
глобални здравствени проблем, посебно у светлу свакодневног повећања броја
имунокомпромитованих особа (ХИВ, дијабетес), онколошких пацијената,
аутоимунских обољења (цистична фиброза, бронхиектазе), и пацијената на
кортикостериоидној терапији или са трансплантацијом органа. Овакве инфекције
су по својој природи најчешће полимикробне и карактеришу се присуством
различитих врста бактерија или бактерија и гљива, који коегзистирају у виду
високо уређених заједница познатих као биофилм.1 Хроничне инфекције се чак у
више од 80% случајева карактеришу постојањем биофилмова, унутар којих су
ћелије патогених микроорганизама заштићене од дејства антимикробних
терапеутика и имунског система, док им је вирулентност доста повећана, што
значајно умањује ефикасност лечења конвенционалним антимикробним лековима.
Додатни изазов у клиничкој пракси представљају ширење антимикробне
резистенције и ограничен број класа антимикробних лекова, као и стагнација
фармацеутске индустрије у развоју иновативних антибиотика са другачијим
механизмом деловања, а посебно антимикотика.1,2 Стога, контрола формирања
биофилма као резервоара инфективних агенаса, и експресије фактора вируленције
патогена који воде ка нарушавању интегритета инфицираних ткива домаћина
представљају један од кључних корака за ефикасан третман хроничних инфекција.
Додатно, примена инхибитора међућелијске комуникације, терапија
бактериофагима, јачање одбрамбеног капацитета имунског система, као и
манипулација целокупним микробиомом представљају само неке од најновијих
приступа у лечењу хроничних инфекција
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Novi pristupi u tretmanu hroničnih bakterijskih i gljivičnih infekcija
T1  - Нови приступи у третману хроничних бактеријских и гљивичних инфекција
SP  - 245
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1745
ER  - 
@conference{
author = "Pavić, Aleksandar",
year = "2022",
abstract = "Hronične infekcije izazvane bakterijama i gljivama predstavljaju rastući
globalni zdravstveni problem, posebno u svetlu svakodnevnog povećanja broja
imunokompromitovanih osoba (HIV, dijabetes), onkoloških pacijenata,
autoimunskih oboljenja (cistična fibroza, bronhiektaze), i pacijenata na
kortikosterioidnoj terapiji ili sa transplantacijom organa. Ovakve infekcije
su po svojoj prirodi najčešće polimikrobne i karakterišu se prisustvom
različitih vrsta bakterija ili bakterija i gljiva, koji koegzistiraju u vidu
visoko uređenih zajednica poznatih kao biofilm.1 Hronične infekcije se čak u
više od 80% slučajeva karakterišu postojanjem biofilmova, unutar kojih su
ćelije patogenih mikroorganizama zaštićene od dejstva antimikrobnih
terapeutika i imunskog sistema, dok im je virulentnost dosta povećana, što
značajno umanjuje efikasnost lečenja konvencionalnim antimikrobnim lekovima.
Dodatni izazov u kliničkoj praksi predstavljaju širenje antimikrobne
rezistencije i ograničen broj klasa antimikrobnih lekova, kao i stagnacija
farmaceutske industrije u razvoju inovativnih antibiotika sa drugačijim
mehanizmom delovanja, a posebno antimikotika.1,2 Stoga, kontrola formiranja
biofilma kao rezervoara infektivnih agenasa, i ekspresije faktora virulencije
patogena koji vode ka narušavanju integriteta inficiranih tkiva domaćina
predstavljaju jedan od ključnih koraka za efikasan tretman hroničnih infekcija.
Dodatno, primena inhibitora međućelijske komunikacije, terapija
bakteriofagima, jačanje odbrambenog kapaciteta imunskog sistema, kao i
manipulacija celokupnim mikrobiomom predstavljaju samo neke od najnovijih
pristupa u lečenju hroničnih infekcija, Хроничне инфекције изазване бактеријама и гљивама представљају растући
глобални здравствени проблем, посебно у светлу свакодневног повећања броја
имунокомпромитованих особа (ХИВ, дијабетес), онколошких пацијената,
аутоимунских обољења (цистична фиброза, бронхиектазе), и пацијената на
кортикостериоидној терапији или са трансплантацијом органа. Овакве инфекције
су по својој природи најчешће полимикробне и карактеришу се присуством
различитих врста бактерија или бактерија и гљива, који коегзистирају у виду
високо уређених заједница познатих као биофилм.1 Хроничне инфекције се чак у
више од 80% случајева карактеришу постојањем биофилмова, унутар којих су
ћелије патогених микроорганизама заштићене од дејства антимикробних
терапеутика и имунског система, док им је вирулентност доста повећана, што
значајно умањује ефикасност лечења конвенционалним антимикробним лековима.
Додатни изазов у клиничкој пракси представљају ширење антимикробне
резистенције и ограничен број класа антимикробних лекова, као и стагнација
фармацеутске индустрије у развоју иновативних антибиотика са другачијим
механизмом деловања, а посебно антимикотика.1,2 Стога, контрола формирања
биофилма као резервоара инфективних агенаса, и експресије фактора вируленције
патогена који воде ка нарушавању интегритета инфицираних ткива домаћина
представљају један од кључних корака за ефикасан третман хроничних инфекција.
Додатно, примена инхибитора међућелијске комуникације, терапија
бактериофагима, јачање одбрамбеног капацитета имунског система, као и
манипулација целокупним микробиомом представљају само неке од најновијих
приступа у лечењу хроничних инфекција",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Novi pristupi u tretmanu hroničnih bakterijskih i gljivičnih infekcija, Нови приступи у третману хроничних бактеријских и гљивичних инфекција",
pages = "245",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1745"
}
Pavić, A.. (2022). Novi pristupi u tretmanu hroničnih bakterijskih i gljivičnih infekcija. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 245.
https://hdl.handle.net/21.15107/rcub_imagine_1745
Pavić A. Novi pristupi u tretmanu hroničnih bakterijskih i gljivičnih infekcija. in Treći kongres biologa Srbije. 2022;:245.
https://hdl.handle.net/21.15107/rcub_imagine_1745 .
Pavić, Aleksandar, "Novi pristupi u tretmanu hroničnih bakterijskih i gljivičnih infekcija" in Treći kongres biologa Srbije (2022):245,
https://hdl.handle.net/21.15107/rcub_imagine_1745 .

Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity (vol 121, 105691, 2022)

Svircev, Milos; Popsavin, Mirjana; Pavić, Aleksandar; Vasiljević, Branka; Rodić, Marko V.; Đokić, Sanja; Kesić, Jelena; Sreco Zelenović, Bojana; Popsavin, Velimir; Kojić, Vesna

(Academic Press Inc Elsevier Science, San Diego, 2022)

TY  - JOUR
AU  - Svircev, Milos
AU  - Popsavin, Mirjana
AU  - Pavić, Aleksandar
AU  - Vasiljević, Branka
AU  - Rodić, Marko V.
AU  - Đokić, Sanja
AU  - Kesić, Jelena
AU  - Sreco Zelenović, Bojana
AU  - Popsavin, Velimir
AU  - Kojić, Vesna
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1582
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Bioorganic Chemistry
T1  - Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity (vol 121, 105691, 2022)
VL  - 127
DO  - 10.1016/j.bioorg.2022.105984
ER  - 
@article{
author = "Svircev, Milos and Popsavin, Mirjana and Pavić, Aleksandar and Vasiljević, Branka and Rodić, Marko V. and Đokić, Sanja and Kesić, Jelena and Sreco Zelenović, Bojana and Popsavin, Velimir and Kojić, Vesna",
year = "2022",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Bioorganic Chemistry",
title = "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity (vol 121, 105691, 2022)",
volume = "127",
doi = "10.1016/j.bioorg.2022.105984"
}
Svircev, M., Popsavin, M., Pavić, A., Vasiljević, B., Rodić, M. V., Đokić, S., Kesić, J., Sreco Zelenović, B., Popsavin, V.,& Kojić, V.. (2022). Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity (vol 121, 105691, 2022). in Bioorganic Chemistry
Academic Press Inc Elsevier Science, San Diego., 127.
https://doi.org/10.1016/j.bioorg.2022.105984
Svircev M, Popsavin M, Pavić A, Vasiljević B, Rodić MV, Đokić S, Kesić J, Sreco Zelenović B, Popsavin V, Kojić V. Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity (vol 121, 105691, 2022). in Bioorganic Chemistry. 2022;127.
doi:10.1016/j.bioorg.2022.105984 .
Svircev, Milos, Popsavin, Mirjana, Pavić, Aleksandar, Vasiljević, Branka, Rodić, Marko V., Đokić, Sanja, Kesić, Jelena, Sreco Zelenović, Bojana, Popsavin, Velimir, Kojić, Vesna, "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity (vol 121, 105691, 2022)" in Bioorganic Chemistry, 127 (2022),
https://doi.org/10.1016/j.bioorg.2022.105984 . .

Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells

Krstić, Aleksandra; Pavić, Aleksandar; Avdović, Edina H.; Marković, Zoran; Stevanović, Milena; Petrović, Isidora

(MDPI, Basel, 2022)

TY  - JOUR
AU  - Krstić, Aleksandra
AU  - Pavić, Aleksandar
AU  - Avdović, Edina H.
AU  - Marković, Zoran
AU  - Stevanović, Milena
AU  - Petrović, Isidora
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1559
AB  - Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 mu M). Treatments induced apoptosis, increased BAX/BCL-2 ratio and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy.
PB  - MDPI, Basel
T2  - Molecules
T1  - Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells
IS  - 7
VL  - 27
DO  - 10.3390/molecules27072115
ER  - 
@article{
author = "Krstić, Aleksandra and Pavić, Aleksandar and Avdović, Edina H. and Marković, Zoran and Stevanović, Milena and Petrović, Isidora",
year = "2022",
abstract = "Pancreatic carcinoma still represents one of the most lethal malignant diseases in the world although some progress has been made in treating the disease in the past decades. Current multi-agent treatment options have improved the overall survival of patients, however, more effective treatment strategies are still needed. In this paper we have characterized the anticancer potential of coumarin-palladium(II) complex against pancreatic carcinoma cells. Cells viability, colony formation and migratory potential of pancreatic carcinoma cells were assessed in vitro, followed by evaluation of apoptosis induction and in vivo testing on zebrafish. Presented results showed remarkable reduction in pancreatic carcinoma cells growth both in vitro and in vivo, being effective at micromolar concentrations (0.5 mu M). Treatments induced apoptosis, increased BAX/BCL-2 ratio and suppressed the expression of SOX9 and SOX18, genes shown to be significantly up-regulated in pancreatic ductal adenocarcinoma. Importantly, treatments of the zebrafish-pancreatic adenocarcinoma xenografts resulted in significant reduction in tumor mass, without provoking any adverse toxic effects including hepatotoxicity. Presented results indicate the great potential of the tested compound and the perspective of its further development towards pancreatic cancer therapy.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells",
number = "7",
volume = "27",
doi = "10.3390/molecules27072115"
}
Krstić, A., Pavić, A., Avdović, E. H., Marković, Z., Stevanović, M.,& Petrović, I.. (2022). Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells. in Molecules
MDPI, Basel., 27(7).
https://doi.org/10.3390/molecules27072115
Krstić A, Pavić A, Avdović EH, Marković Z, Stevanović M, Petrović I. Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells. in Molecules. 2022;27(7).
doi:10.3390/molecules27072115 .
Krstić, Aleksandra, Pavić, Aleksandar, Avdović, Edina H., Marković, Zoran, Stevanović, Milena, Petrović, Isidora, "Coumarin-Palladium(II) Complex Acts as a Potent and Non-Toxic Anticancer Agent against Pancreatic Carcinoma Cells" in Molecules, 27, no. 7 (2022),
https://doi.org/10.3390/molecules27072115 . .
5
6

Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model

Pavić, Aleksandar; Stojanović, Zoran; Pekmezović, Marina; Veljović, Đorđe; O'Connor, Kevin; Malagurski, Ivana; Nikodinović-Runić, Jasmina

(MDPI, Basel, 2022)

TY  - JOUR
AU  - Pavić, Aleksandar
AU  - Stojanović, Zoran
AU  - Pekmezović, Marina
AU  - Veljović, Đorđe
AU  - O'Connor, Kevin
AU  - Malagurski, Ivana
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1554
AB  - Immobilizing antifungal polyenes such as nystatin (Nys) and amphotericin B (AmB) into biodegradable formulations is advantageous compared to free drug administration providing sustained release, reduced dosing due to localized targeting and overall reduced systemic drug toxicity. In this study, we encapsulated Nys and AmB in medium chain length polyhydroxyalkanoates (mcl-PHA) microspheres (7-8 mu m in diameter). The obtained formulations have been validated for antifungal activity in vitro against a panel of pathogenic fungi including species of Candida, Aspergillus, Microsporum and Trichophyton genera and toxicity and efficacy in vivo using the zebrafish model of disseminated candidiasis. While free polyenes, especially AmB, were highly toxic to zebrafish embryos at the effective (MIC) doses, after their loading into mcl-PHA microspheres, inner organ toxicity and teratogenicity associated with both drugs were not observed, even at 100 x MIC doses. The obtained mcl-PHA/polyene formulations have successfully eradicated C. albicans infection and showed an improved therapeutic profile in zebrafish by enhancing infected embryos survival. This approach is contributing to the antifungal arsenal as polyenes, although the first broad-spectrum antifungals on the market are still the gold standard for treatment of fungal infections.
PB  - MDPI, Basel
T2  - Pharmaceutics
T1  - Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model
IS  - 4
VL  - 14
DO  - 10.3390/pharmaceutics14040696
ER  - 
@article{
author = "Pavić, Aleksandar and Stojanović, Zoran and Pekmezović, Marina and Veljović, Đorđe and O'Connor, Kevin and Malagurski, Ivana and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "Immobilizing antifungal polyenes such as nystatin (Nys) and amphotericin B (AmB) into biodegradable formulations is advantageous compared to free drug administration providing sustained release, reduced dosing due to localized targeting and overall reduced systemic drug toxicity. In this study, we encapsulated Nys and AmB in medium chain length polyhydroxyalkanoates (mcl-PHA) microspheres (7-8 mu m in diameter). The obtained formulations have been validated for antifungal activity in vitro against a panel of pathogenic fungi including species of Candida, Aspergillus, Microsporum and Trichophyton genera and toxicity and efficacy in vivo using the zebrafish model of disseminated candidiasis. While free polyenes, especially AmB, were highly toxic to zebrafish embryos at the effective (MIC) doses, after their loading into mcl-PHA microspheres, inner organ toxicity and teratogenicity associated with both drugs were not observed, even at 100 x MIC doses. The obtained mcl-PHA/polyene formulations have successfully eradicated C. albicans infection and showed an improved therapeutic profile in zebrafish by enhancing infected embryos survival. This approach is contributing to the antifungal arsenal as polyenes, although the first broad-spectrum antifungals on the market are still the gold standard for treatment of fungal infections.",
publisher = "MDPI, Basel",
journal = "Pharmaceutics",
title = "Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model",
number = "4",
volume = "14",
doi = "10.3390/pharmaceutics14040696"
}
Pavić, A., Stojanović, Z., Pekmezović, M., Veljović, Đ., O'Connor, K., Malagurski, I.,& Nikodinović-Runić, J.. (2022). Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model. in Pharmaceutics
MDPI, Basel., 14(4).
https://doi.org/10.3390/pharmaceutics14040696
Pavić A, Stojanović Z, Pekmezović M, Veljović Đ, O'Connor K, Malagurski I, Nikodinović-Runić J. Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model. in Pharmaceutics. 2022;14(4).
doi:10.3390/pharmaceutics14040696 .
Pavić, Aleksandar, Stojanović, Zoran, Pekmezović, Marina, Veljović, Đorđe, O'Connor, Kevin, Malagurski, Ivana, Nikodinović-Runić, Jasmina, "Polyenes in Medium Chain Length Polyhydroxyalkanoate (mcl-PHA) Biopolymer Microspheres with Reduced Toxicity and Improved Therapeutic Effect against Candida Infection in Zebrafish Model" in Pharmaceutics, 14, no. 4 (2022),
https://doi.org/10.3390/pharmaceutics14040696 . .
7
5

Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding

Schindler, Kevin; Cortat, Youri; Nedyalkova, Miroslava; Crochet, Aurelien; Lattuada, Marco; Pavić, Aleksandar; Zobi, Fabio

(MDPI, Basel, 2022)

TY  - JOUR
AU  - Schindler, Kevin
AU  - Cortat, Youri
AU  - Nedyalkova, Miroslava
AU  - Crochet, Aurelien
AU  - Lattuada, Marco
AU  - Pavić, Aleksandar
AU  - Zobi, Fabio
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1528
AB  - Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the antimicrobial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics.
PB  - MDPI, Basel
T2  - Pharmaceuticals
T1  - Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding
IS  - 9
VL  - 15
DO  - 10.3390/ph15091107
ER  - 
@article{
author = "Schindler, Kevin and Cortat, Youri and Nedyalkova, Miroslava and Crochet, Aurelien and Lattuada, Marco and Pavić, Aleksandar and Zobi, Fabio",
year = "2022",
abstract = "Antimicrobial resistance is one of the major human health threats, with significant impacts on the global economy. Antibiotics are becoming increasingly ineffective as drug-resistance spreads, imposing an urgent need for new and innovative antimicrobial agents. Metal complexes are an untapped source of antimicrobial potential. Rhenium complexes, amongst others, are particularly attractive due to their low in vivo toxicity and high antimicrobial activity, but little is known about their targets and mechanism of action. In this study, a series of rhenium di- and tricarbonyl diimine complexes were prepared and evaluated for their antimicrobial potential against eight different microorganisms comprising Gram-negative and -positive bacteria. Our data showed that none of the Re dicarbonyl or neutral tricarbonyl species have either bactericidal or bacteriostatic potential. In order to identify possible targets of the molecules, and thus possibly understand the observed differences in the antimicrobial efficacy of the molecules, we computationally evaluated the binding affinity of active and inactive complexes against structurally characterized membrane-bound S. aureus proteins. The computational analysis indicates two possible major targets for this class of compounds, namely lipoteichoic acids flippase (LtaA) and lipoprotein signal peptidase II (LspA). Our results, consistent with the published in vitro studies, will be useful for the future design of rhenium tricarbonyl diimine-based antibiotics.",
publisher = "MDPI, Basel",
journal = "Pharmaceuticals",
title = "Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding",
number = "9",
volume = "15",
doi = "10.3390/ph15091107"
}
Schindler, K., Cortat, Y., Nedyalkova, M., Crochet, A., Lattuada, M., Pavić, A.,& Zobi, F.. (2022). Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding. in Pharmaceuticals
MDPI, Basel., 15(9).
https://doi.org/10.3390/ph15091107
Schindler K, Cortat Y, Nedyalkova M, Crochet A, Lattuada M, Pavić A, Zobi F. Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding. in Pharmaceuticals. 2022;15(9).
doi:10.3390/ph15091107 .
Schindler, Kevin, Cortat, Youri, Nedyalkova, Miroslava, Crochet, Aurelien, Lattuada, Marco, Pavić, Aleksandar, Zobi, Fabio, "Antimicrobial Activity of Rhenium Di- and Tricarbonyl Diimine Complexes: Insights on Membrane-Bound S. aureus Protein Binding" in Pharmaceuticals, 15, no. 9 (2022),
https://doi.org/10.3390/ph15091107 . .
1
8
7

Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo

Đokić, Lidija; Stanković, Nada; Galić, Ivana; Morić, Ivana; Radaković, Nataša; Segan, Sandra; Pavić, Aleksandar; Šenerović, Lidija

(Frontiers Media Sa, Lausanne, 2022)

TY  - JOUR
AU  - Đokić, Lidija
AU  - Stanković, Nada
AU  - Galić, Ivana
AU  - Morić, Ivana
AU  - Radaković, Nataša
AU  - Segan, Sandra
AU  - Pavić, Aleksandar
AU  - Šenerović, Lidija
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1596
AB  - Bacterial infections have become increasingly difficult to treat due to the occurrence of antibiotic-resistant strains. A promising strategy to increase the efficacy of therapy is to combine antibacterials with agents that decrease pathogen virulence via the modulation of the quorum sensing (QS). Lactonases inhibit acylated homoserine lactone (AHL)-mediated QS in Gram-negative bacteria, including the leading nosocomial pathogen Pseudomonas aeruginosa. Here we describe the characteristics of heterologously expressed YtnP lactonase from Bacillus paralicheniformis ZP1 (YtnP-ZP1) isolated from agricultural soil using the culture enrichment method. Purified YtnP-ZP1 hydrolyzed different AHLs with preference to substrates with long acyl residues as evaluated in assays with biosensors and HPLC. The enzyme showed good thermostability and activity in a wide temperature range. YtnP-ZP1 in 50 mu g mL(-1) concentration reduced the amount of P. aeruginosa-produced long-chain AHLs by 85%, while it hydrolyzed 50% of short-chain AHLs. Incubation of P. aeruginosa PAO1 with YtnP-ZP1 reduced its swarming motility and elastolytic activity without bactericidal effect. YtnP-ZP1 caused the inhibition of biofilm formation and disintegration of mature biofilms in P. aeruginosa PAO1 and multiresistant clinical strain BR5H that was visualized by crystal violet staining. The treatment with YtnP-ZP1 in concentrations higher than 25 mu g mL(-1) improved the survival of P. aeruginosa PAO1-infected zebrafish (Danio rerio), rescuing 80% of embryos, while in combination with tobramycin or gentamicin survival rate increased to 100%. The treatment of P. aeruginosa PAO1 biofilms on infected zebrafish tail wounds with 50 mu g mL(-1) YtnP-ZP1 and 2 x MIC tobramycin led to infection clearing in 2 days. The extensive toxicity studies proved YtnP-ZP1 was non-toxic to human cells and zebrafish. In conclusion, novel YtnP-ZP1 lactonase with its effective anti-virulence activity could be used to increase the efficacy of clinically approved antibiotics in clearing both systemic and biofilm-associated P. aeruginosa infections.
PB  - Frontiers Media Sa, Lausanne
T2  - Frontiers in Microbiology
T1  - Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo
VL  - 13
DO  - 10.3389/fmicb.2022.906312
ER  - 
@article{
author = "Đokić, Lidija and Stanković, Nada and Galić, Ivana and Morić, Ivana and Radaković, Nataša and Segan, Sandra and Pavić, Aleksandar and Šenerović, Lidija",
year = "2022",
abstract = "Bacterial infections have become increasingly difficult to treat due to the occurrence of antibiotic-resistant strains. A promising strategy to increase the efficacy of therapy is to combine antibacterials with agents that decrease pathogen virulence via the modulation of the quorum sensing (QS). Lactonases inhibit acylated homoserine lactone (AHL)-mediated QS in Gram-negative bacteria, including the leading nosocomial pathogen Pseudomonas aeruginosa. Here we describe the characteristics of heterologously expressed YtnP lactonase from Bacillus paralicheniformis ZP1 (YtnP-ZP1) isolated from agricultural soil using the culture enrichment method. Purified YtnP-ZP1 hydrolyzed different AHLs with preference to substrates with long acyl residues as evaluated in assays with biosensors and HPLC. The enzyme showed good thermostability and activity in a wide temperature range. YtnP-ZP1 in 50 mu g mL(-1) concentration reduced the amount of P. aeruginosa-produced long-chain AHLs by 85%, while it hydrolyzed 50% of short-chain AHLs. Incubation of P. aeruginosa PAO1 with YtnP-ZP1 reduced its swarming motility and elastolytic activity without bactericidal effect. YtnP-ZP1 caused the inhibition of biofilm formation and disintegration of mature biofilms in P. aeruginosa PAO1 and multiresistant clinical strain BR5H that was visualized by crystal violet staining. The treatment with YtnP-ZP1 in concentrations higher than 25 mu g mL(-1) improved the survival of P. aeruginosa PAO1-infected zebrafish (Danio rerio), rescuing 80% of embryos, while in combination with tobramycin or gentamicin survival rate increased to 100%. The treatment of P. aeruginosa PAO1 biofilms on infected zebrafish tail wounds with 50 mu g mL(-1) YtnP-ZP1 and 2 x MIC tobramycin led to infection clearing in 2 days. The extensive toxicity studies proved YtnP-ZP1 was non-toxic to human cells and zebrafish. In conclusion, novel YtnP-ZP1 lactonase with its effective anti-virulence activity could be used to increase the efficacy of clinically approved antibiotics in clearing both systemic and biofilm-associated P. aeruginosa infections.",
publisher = "Frontiers Media Sa, Lausanne",
journal = "Frontiers in Microbiology",
title = "Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo",
volume = "13",
doi = "10.3389/fmicb.2022.906312"
}
Đokić, L., Stanković, N., Galić, I., Morić, I., Radaković, N., Segan, S., Pavić, A.,& Šenerović, L.. (2022). Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo. in Frontiers in Microbiology
Frontiers Media Sa, Lausanne., 13.
https://doi.org/10.3389/fmicb.2022.906312
Đokić L, Stanković N, Galić I, Morić I, Radaković N, Segan S, Pavić A, Šenerović L. Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo. in Frontiers in Microbiology. 2022;13.
doi:10.3389/fmicb.2022.906312 .
Đokić, Lidija, Stanković, Nada, Galić, Ivana, Morić, Ivana, Radaković, Nataša, Segan, Sandra, Pavić, Aleksandar, Šenerović, Lidija, "Novel Quorum Quenching YtnP Lactonase From Bacillus paralicheniformis Reduces Pseudomonas aeruginosa Virulence and Increases Antibiotic Efficacy in vivo" in Frontiers in Microbiology, 13 (2022),
https://doi.org/10.3389/fmicb.2022.906312 . .
3
12
11

Biocompatibility and antibiofilm activity of graphene-oxide functionalized titanium discs and collagen membranes

Radunović, Milena; Pavić, Aleksandar; Ivanović, Vera; Milivojević, Marija; Radović, Igor; Di Carlo, Roberta; Pilato, Serena; Fontana, Antonella; Piattelli, Adriano; Petrović, Sanja

(Elsevier Sci Ltd, Oxford, 2022)

TY  - JOUR
AU  - Radunović, Milena
AU  - Pavić, Aleksandar
AU  - Ivanović, Vera
AU  - Milivojević, Marija
AU  - Radović, Igor
AU  - Di Carlo, Roberta
AU  - Pilato, Serena
AU  - Fontana, Antonella
AU  - Piattelli, Adriano
AU  - Petrović, Sanja
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1511
AB  - The aims of the study were: 1) to evaluate the effect on biofilm formation of barrier membranes and titanium surfaces coated with graphene-oxide (GO); 2) to analyze the connection between the superficial topography of the tested materials and the amount of bacterial accumulation on them and 3) to analyze the biocompatibility of GO functionalized discs using the zebrafish model. Methods: Single species bacterial biofilms (Streptococcus oralis, Veilonella parvula, Fusobacterium nucleatum, Porphyomonas gingivalis) were grown on GO-free membranes, membranes coated with 2 and 10 mu g/ml of GO, GO-free and GO-coated titanium discs. The biofilms were analyzed by determining the CFU count and by Scanning Electron Microscopy (SEM) and the materials' topography by Atomic Force Microscopy (AFM). Zebrafish model was used to determine the materials' toxicity and inflammatory effects. Results: AFM showed similar roughness of control and GO-coated materials. CFU counts on GO-coated discs were significantly lower than on control discs for all species. CFU counts of S. oralis, V. parvula and P. gingivalis were lower on biofilms grown on both types of GOcoated membranes than on GO-free membrane. SEM analysis showed different formation of single species biofilm of S. oralis on control and GO-coated materials. GO-functionalized titanium discs do not induce toxic or inflammatory effects. Significance: Titanium implant surfaces functionalized with GO have shown to be biocompatible and less susceptible to biofilm formation. These results encourage further in vivo investigation of the tested materials on infection prevention, specifically in prevention and reduction of peri-implant mucositis and periimplantitis incidence.
PB  - Elsevier Sci Ltd, Oxford
T2  - Dental Materials
T1  - Biocompatibility and antibiofilm activity of graphene-oxide functionalized titanium discs and collagen membranes
EP  - 1127
IS  - 7
SP  - 1117
VL  - 38
DO  - 10.1016/j.dental.2022.04.024
ER  - 
@article{
author = "Radunović, Milena and Pavić, Aleksandar and Ivanović, Vera and Milivojević, Marija and Radović, Igor and Di Carlo, Roberta and Pilato, Serena and Fontana, Antonella and Piattelli, Adriano and Petrović, Sanja",
year = "2022",
abstract = "The aims of the study were: 1) to evaluate the effect on biofilm formation of barrier membranes and titanium surfaces coated with graphene-oxide (GO); 2) to analyze the connection between the superficial topography of the tested materials and the amount of bacterial accumulation on them and 3) to analyze the biocompatibility of GO functionalized discs using the zebrafish model. Methods: Single species bacterial biofilms (Streptococcus oralis, Veilonella parvula, Fusobacterium nucleatum, Porphyomonas gingivalis) were grown on GO-free membranes, membranes coated with 2 and 10 mu g/ml of GO, GO-free and GO-coated titanium discs. The biofilms were analyzed by determining the CFU count and by Scanning Electron Microscopy (SEM) and the materials' topography by Atomic Force Microscopy (AFM). Zebrafish model was used to determine the materials' toxicity and inflammatory effects. Results: AFM showed similar roughness of control and GO-coated materials. CFU counts on GO-coated discs were significantly lower than on control discs for all species. CFU counts of S. oralis, V. parvula and P. gingivalis were lower on biofilms grown on both types of GOcoated membranes than on GO-free membrane. SEM analysis showed different formation of single species biofilm of S. oralis on control and GO-coated materials. GO-functionalized titanium discs do not induce toxic or inflammatory effects. Significance: Titanium implant surfaces functionalized with GO have shown to be biocompatible and less susceptible to biofilm formation. These results encourage further in vivo investigation of the tested materials on infection prevention, specifically in prevention and reduction of peri-implant mucositis and periimplantitis incidence.",
publisher = "Elsevier Sci Ltd, Oxford",
journal = "Dental Materials",
title = "Biocompatibility and antibiofilm activity of graphene-oxide functionalized titanium discs and collagen membranes",
pages = "1127-1117",
number = "7",
volume = "38",
doi = "10.1016/j.dental.2022.04.024"
}
Radunović, M., Pavić, A., Ivanović, V., Milivojević, M., Radović, I., Di Carlo, R., Pilato, S., Fontana, A., Piattelli, A.,& Petrović, S.. (2022). Biocompatibility and antibiofilm activity of graphene-oxide functionalized titanium discs and collagen membranes. in Dental Materials
Elsevier Sci Ltd, Oxford., 38(7), 1117-1127.
https://doi.org/10.1016/j.dental.2022.04.024
Radunović M, Pavić A, Ivanović V, Milivojević M, Radović I, Di Carlo R, Pilato S, Fontana A, Piattelli A, Petrović S. Biocompatibility and antibiofilm activity of graphene-oxide functionalized titanium discs and collagen membranes. in Dental Materials. 2022;38(7):1117-1127.
doi:10.1016/j.dental.2022.04.024 .
Radunović, Milena, Pavić, Aleksandar, Ivanović, Vera, Milivojević, Marija, Radović, Igor, Di Carlo, Roberta, Pilato, Serena, Fontana, Antonella, Piattelli, Adriano, Petrović, Sanja, "Biocompatibility and antibiofilm activity of graphene-oxide functionalized titanium discs and collagen membranes" in Dental Materials, 38, no. 7 (2022):1117-1127,
https://doi.org/10.1016/j.dental.2022.04.024 . .
1
4
4

Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity

Svircev, Milos; Popsavin, Mirjana; Pavić, Aleksandar; Vasiljević, Branka; Rodić, Marko V.; Đokić, Sanja; Kesić, Jelena; Sreco Zelenović, Bojana; Popsavin, Velimir; Kojić, Vesna

(Academic Press Inc Elsevier Science, San Diego, 2022)

TY  - JOUR
AU  - Svircev, Milos
AU  - Popsavin, Mirjana
AU  - Pavić, Aleksandar
AU  - Vasiljević, Branka
AU  - Rodić, Marko V.
AU  - Đokić, Sanja
AU  - Kesić, Jelena
AU  - Sreco Zelenović, Bojana
AU  - Popsavin, Velimir
AU  - Kojić, Vesna
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1561
AB  - The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Bioorganic Chemistry
T1  - Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity
VL  - 121
DO  - 10.1016/j.bioorg.2022.105691
ER  - 
@article{
author = "Svircev, Milos and Popsavin, Mirjana and Pavić, Aleksandar and Vasiljević, Branka and Rodić, Marko V. and Đokić, Sanja and Kesić, Jelena and Sreco Zelenović, Bojana and Popsavin, Velimir and Kojić, Vesna",
year = "2022",
abstract = "The synthesis of several new goniofufurone bioisosteres was achieved in which the phenyl residue was replaced by a thiazole ring. The key steps of the synthesis included the initial condensation of cyanohydrin benzoates with cysteine ethyl ester hydrochloride, followed by the subsequent reaction of resulting C-4 ' epimeric thiazolines with DBU, to introduce 5-deoxy functionality and to elaborate the thiazole ring in one step. Synthesized compounds showed potent growth inhibitory effects against selected human tumour cell lines, especially bioisostere 4, which in the culture of MCF-7 cells displayed the highest activity (IC50 = 0.19 nM) of all compounds under evaluation. This molecule exhibited 64474-fold higher antiproliferative activity than lead 2 and was1053-fold more active than the commercial antitumour agent doxorubicin in the culture of MCF-7 cells. The structural features of the tested compounds responsible for their antiproliferative activity have been identified by preliminary SAR analysis. The toxicity of the most active compound 4 was assessed by an in vivo experiment in a zebrafish model (Danio rerio), whereupon it was found non-toxic at any of the tested concentrations up to 125 mu M.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Bioorganic Chemistry",
title = "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity",
volume = "121",
doi = "10.1016/j.bioorg.2022.105691"
}
Svircev, M., Popsavin, M., Pavić, A., Vasiljević, B., Rodić, M. V., Đokić, S., Kesić, J., Sreco Zelenović, B., Popsavin, V.,& Kojić, V.. (2022). Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity. in Bioorganic Chemistry
Academic Press Inc Elsevier Science, San Diego., 121.
https://doi.org/10.1016/j.bioorg.2022.105691
Svircev M, Popsavin M, Pavić A, Vasiljević B, Rodić MV, Đokić S, Kesić J, Sreco Zelenović B, Popsavin V, Kojić V. Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity. in Bioorganic Chemistry. 2022;121.
doi:10.1016/j.bioorg.2022.105691 .
Svircev, Milos, Popsavin, Mirjana, Pavić, Aleksandar, Vasiljević, Branka, Rodić, Marko V., Đokić, Sanja, Kesić, Jelena, Sreco Zelenović, Bojana, Popsavin, Velimir, Kojić, Vesna, "Design, synthesis, and biological evaluation of thiazole bioisosteres of goniofufurone through in vitro antiproliferative activity and in vivo toxicity" in Bioorganic Chemistry, 121 (2022),
https://doi.org/10.1016/j.bioorg.2022.105691 . .
6
5

Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis

Radaković, Nataša; Nikolić, Andrea; Terzić-Jovanović, Nataša; Stojković, Pavle; Stanković, Nada; Solaja, Bogdan; Opsenica, Igor; Pavić, Aleksandar

(Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux, 2022)

TY  - JOUR
AU  - Radaković, Nataša
AU  - Nikolić, Andrea
AU  - Terzić-Jovanović, Nataša
AU  - Stojković, Pavle
AU  - Stanković, Nada
AU  - Solaja, Bogdan
AU  - Opsenica, Igor
AU  - Pavić, Aleksandar
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1593
AB  - Candida albicans remains the main causal agent of candidiasis, the most common fungal infection with disturbingly high mortality rates worldwide. The limited diversity and efficacy of clinical antifungal drugs, exacerbated by emerging drug resistance, have resulted in the failure of current antifungal therapies. This imposes an urgent demand for the development of innovative strategies for effective eradication of candidal infections. While the existing clinical drugs display fungicidal or fungistatic activity, the strategy specifically targeting C. albicans filamentation, as the most important virulence trait, represents an attractive approach for overcoming the drawbacks related to clinical antifungals. The results acquired in this study revealed the significant potential of 5-aminotetrazoles as a new class of effective and safe anti-virulence agents. Moreover, these novel agents were active when applied both alone and in combination with clinically approved polyenes. Complete prevention of C. albicans morphogenetic yeast-to-hyphae transition was achieved at doses as low as 1.3 mM under conditions mimicking various filamentation-responsive stimuli in the human body, while no cardio-or hepatotoxicity was observed at doses as high as 200 mM. The treatment of C. albicans-infected zebrafish embryos with nystatin alone had low efficacy, while the combination of nystatin and selected 5aminotetrazoles prevented fungal filamentation, successfully eliminating the infection and rescuing the infected embryos from lethal disseminated candidiasis. In addition, the most potent anti-virulence 5aminotetrazole prevented C. albicans in developing the resistance to nystatin when applied in combination, keeping the fungus sensitive to the antifungal drug.
PB  - Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux
T2  - European Journal of Medicinal Chemistry
T1  - Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis
VL  - 230
DO  - 10.1016/j.ejmech.2022.114137
ER  - 
@article{
author = "Radaković, Nataša and Nikolić, Andrea and Terzić-Jovanović, Nataša and Stojković, Pavle and Stanković, Nada and Solaja, Bogdan and Opsenica, Igor and Pavić, Aleksandar",
year = "2022",
abstract = "Candida albicans remains the main causal agent of candidiasis, the most common fungal infection with disturbingly high mortality rates worldwide. The limited diversity and efficacy of clinical antifungal drugs, exacerbated by emerging drug resistance, have resulted in the failure of current antifungal therapies. This imposes an urgent demand for the development of innovative strategies for effective eradication of candidal infections. While the existing clinical drugs display fungicidal or fungistatic activity, the strategy specifically targeting C. albicans filamentation, as the most important virulence trait, represents an attractive approach for overcoming the drawbacks related to clinical antifungals. The results acquired in this study revealed the significant potential of 5-aminotetrazoles as a new class of effective and safe anti-virulence agents. Moreover, these novel agents were active when applied both alone and in combination with clinically approved polyenes. Complete prevention of C. albicans morphogenetic yeast-to-hyphae transition was achieved at doses as low as 1.3 mM under conditions mimicking various filamentation-responsive stimuli in the human body, while no cardio-or hepatotoxicity was observed at doses as high as 200 mM. The treatment of C. albicans-infected zebrafish embryos with nystatin alone had low efficacy, while the combination of nystatin and selected 5aminotetrazoles prevented fungal filamentation, successfully eliminating the infection and rescuing the infected embryos from lethal disseminated candidiasis. In addition, the most potent anti-virulence 5aminotetrazole prevented C. albicans in developing the resistance to nystatin when applied in combination, keeping the fungus sensitive to the antifungal drug.",
publisher = "Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux",
journal = "European Journal of Medicinal Chemistry",
title = "Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis",
volume = "230",
doi = "10.1016/j.ejmech.2022.114137"
}
Radaković, N., Nikolić, A., Terzić-Jovanović, N., Stojković, P., Stanković, N., Solaja, B., Opsenica, I.,& Pavić, A.. (2022). Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis. in European Journal of Medicinal Chemistry
Elsevier France-Editions Scientifiques Medicales Elsevier, Issy-Les-Moulineaux., 230.
https://doi.org/10.1016/j.ejmech.2022.114137
Radaković N, Nikolić A, Terzić-Jovanović N, Stojković P, Stanković N, Solaja B, Opsenica I, Pavić A. Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis. in European Journal of Medicinal Chemistry. 2022;230.
doi:10.1016/j.ejmech.2022.114137 .
Radaković, Nataša, Nikolić, Andrea, Terzić-Jovanović, Nataša, Stojković, Pavle, Stanković, Nada, Solaja, Bogdan, Opsenica, Igor, Pavić, Aleksandar, "Unraveling the anti-virulence potential and antifungal efficacy of 5-aminotetrazoles using the zebrafish model of disseminated candidiasis" in European Journal of Medicinal Chemistry, 230 (2022),
https://doi.org/10.1016/j.ejmech.2022.114137 . .
2
4
4

Unravelling Anti-Melanogenic Potency of Edible Mushrooms Laetiporus sulphureus and Agaricus silvaticus In Vivo Using the Zebrafish Model

Pavić, Aleksandar; Ilić-Tomić, Tatjana; Glamoclija, Jasmina

(MDPI, Basel, 2021)

TY  - JOUR
AU  - Pavić, Aleksandar
AU  - Ilić-Tomić, Tatjana
AU  - Glamoclija, Jasmina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1474
AB  - Severe drawbacks associated with the topical use of depigmenting agents in treatments of skin hyperigmentations impose a great demand for novel, effective, and safe melanogenesis inhibitors. Edible and medicinal mushrooms, known for numerous health-promoting properties, represent a rich reservoir of anti-melanogenic compounds, with the potential to be applied in preventing excessive skin pigmentation. Herein, using zebrafish (Danio rerio) as a preclinical animal model, we have demonstrated that ethanol extract of Laetiporus sulphureus (LSE) and Agaricus silvaticus (ASE) are not toxic at high doses up to 400-500 mu g/mL while effectively inhibit melanogenesis in a dose-dependent manner. At depigmenting doses, the explored extracts showed no adverse effects on zebrafish embryos melanocytes. Even more, they did not provoke inflammation or neutropenia when applied at the highest dose ensuring almost complete the cells depigmentation. Since LSE and ASE have demonstrated significantly higher the therapeutic potential than kojic acid and hydroquinone, two well-known depigmenting agents, overall results of this study strongly suggest that the explored mushrooms extracts could be used as efficient and safe topical agents in treatments of skin hyperpigmentation disorders.
PB  - MDPI, Basel
T2  - Journal of Fungi
T1  - Unravelling Anti-Melanogenic Potency of Edible Mushrooms Laetiporus sulphureus and Agaricus silvaticus In Vivo Using the Zebrafish Model
IS  - 10
VL  - 7
DO  - 10.3390/jof7100834
ER  - 
@article{
author = "Pavić, Aleksandar and Ilić-Tomić, Tatjana and Glamoclija, Jasmina",
year = "2021",
abstract = "Severe drawbacks associated with the topical use of depigmenting agents in treatments of skin hyperigmentations impose a great demand for novel, effective, and safe melanogenesis inhibitors. Edible and medicinal mushrooms, known for numerous health-promoting properties, represent a rich reservoir of anti-melanogenic compounds, with the potential to be applied in preventing excessive skin pigmentation. Herein, using zebrafish (Danio rerio) as a preclinical animal model, we have demonstrated that ethanol extract of Laetiporus sulphureus (LSE) and Agaricus silvaticus (ASE) are not toxic at high doses up to 400-500 mu g/mL while effectively inhibit melanogenesis in a dose-dependent manner. At depigmenting doses, the explored extracts showed no adverse effects on zebrafish embryos melanocytes. Even more, they did not provoke inflammation or neutropenia when applied at the highest dose ensuring almost complete the cells depigmentation. Since LSE and ASE have demonstrated significantly higher the therapeutic potential than kojic acid and hydroquinone, two well-known depigmenting agents, overall results of this study strongly suggest that the explored mushrooms extracts could be used as efficient and safe topical agents in treatments of skin hyperpigmentation disorders.",
publisher = "MDPI, Basel",
journal = "Journal of Fungi",
title = "Unravelling Anti-Melanogenic Potency of Edible Mushrooms Laetiporus sulphureus and Agaricus silvaticus In Vivo Using the Zebrafish Model",
number = "10",
volume = "7",
doi = "10.3390/jof7100834"
}
Pavić, A., Ilić-Tomić, T.,& Glamoclija, J.. (2021). Unravelling Anti-Melanogenic Potency of Edible Mushrooms Laetiporus sulphureus and Agaricus silvaticus In Vivo Using the Zebrafish Model. in Journal of Fungi
MDPI, Basel., 7(10).
https://doi.org/10.3390/jof7100834
Pavić A, Ilić-Tomić T, Glamoclija J. Unravelling Anti-Melanogenic Potency of Edible Mushrooms Laetiporus sulphureus and Agaricus silvaticus In Vivo Using the Zebrafish Model. in Journal of Fungi. 2021;7(10).
doi:10.3390/jof7100834 .
Pavić, Aleksandar, Ilić-Tomić, Tatjana, Glamoclija, Jasmina, "Unravelling Anti-Melanogenic Potency of Edible Mushrooms Laetiporus sulphureus and Agaricus silvaticus In Vivo Using the Zebrafish Model" in Journal of Fungi, 7, no. 10 (2021),
https://doi.org/10.3390/jof7100834 . .
8
8

Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release

Sovari, Sara Nasiri; Kolly, Isabelle; Schindler, Kevin; Cortat, Youri; Liu, Shing-Chi; Crochet, Aurelien; Pavić, Aleksandar; Zobi, Fabio

(MDPI, Basel, 2021)

TY  - JOUR
AU  - Sovari, Sara Nasiri
AU  - Kolly, Isabelle
AU  - Schindler, Kevin
AU  - Cortat, Youri
AU  - Liu, Shing-Chi
AU  - Crochet, Aurelien
AU  - Pavić, Aleksandar
AU  - Zobi, Fabio
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1459
AB  - The reaction of rhenium alpha-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)(2)(NO)(N-N)X](+) species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)(2)(NO)(N-N)X](+) is that of a hard Re acid, probably due to the stronger pi-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for pi-basic ligands, which are consequently difficult to replace by, e.g., sigma-donor or weak pi-acids like pyridine. Attempts of direct nitrosylation of alpha-diimine fac-[Re(CO)(3)](+) complexes bearing pi-basic OR-type ligands gave the [Re(CO)(2)(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)(2)(NO)(N-N)X](+) complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.
PB  - MDPI, Basel
T2  - Molecules
T1  - Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release
IS  - 17
VL  - 26
DO  - 10.3390/molecules26175302
ER  - 
@article{
author = "Sovari, Sara Nasiri and Kolly, Isabelle and Schindler, Kevin and Cortat, Youri and Liu, Shing-Chi and Crochet, Aurelien and Pavić, Aleksandar and Zobi, Fabio",
year = "2021",
abstract = "The reaction of rhenium alpha-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)(2)(NO)(N-N)X](+) species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)(2)(NO)(N-N)X](+) is that of a hard Re acid, probably due to the stronger pi-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for pi-basic ligands, which are consequently difficult to replace by, e.g., sigma-donor or weak pi-acids like pyridine. Attempts of direct nitrosylation of alpha-diimine fac-[Re(CO)(3)](+) complexes bearing pi-basic OR-type ligands gave the [Re(CO)(2)(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)(2)(NO)(N-N)X](+) complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release",
number = "17",
volume = "26",
doi = "10.3390/molecules26175302"
}
Sovari, S. N., Kolly, I., Schindler, K., Cortat, Y., Liu, S., Crochet, A., Pavić, A.,& Zobi, F.. (2021). Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release. in Molecules
MDPI, Basel., 26(17).
https://doi.org/10.3390/molecules26175302
Sovari SN, Kolly I, Schindler K, Cortat Y, Liu S, Crochet A, Pavić A, Zobi F. Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release. in Molecules. 2021;26(17).
doi:10.3390/molecules26175302 .
Sovari, Sara Nasiri, Kolly, Isabelle, Schindler, Kevin, Cortat, Youri, Liu, Shing-Chi, Crochet, Aurelien, Pavić, Aleksandar, Zobi, Fabio, "Efficient Direct Nitrosylation of alpha-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release" in Molecules, 26, no. 17 (2021),
https://doi.org/10.3390/molecules26175302 . .
3
3

Improvement of the anti-Candida activity of itraconazole in the zebrafish infection model by its coordination to silver(I)

Stevanović, Nevena Lj.; Glišić, Biljana; Vojnović, Sandra; Wadepohl, Hubert; Andrejević, Tina P.; Durić, Sonja Z.; Savić, Nada D.; Nikodinović-Runić, Jasmina; Djuran, Milos ; Pavić, Aleksandar

(Elsevier, Amsterdam, 2021)

TY  - JOUR
AU  - Stevanović, Nevena Lj.
AU  - Glišić, Biljana
AU  - Vojnović, Sandra
AU  - Wadepohl, Hubert
AU  - Andrejević, Tina P.
AU  - Durić, Sonja Z.
AU  - Savić, Nada D.
AU  - Nikodinović-Runić, Jasmina
AU  - Djuran, Milos 
AU  - Pavić, Aleksandar
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1424
AB  - In order to develop a novel antifungal agent, we synthesized and completely structurally characterized the silver(I) complex with the known antimycotic itraconazole (itraco), [Ag(itraco-N)(2)]NO3 center dot H2O (Agitraco). The spectroscopic and crystallographic results revealed that, in this complex, two itraco ligands are monodentately coordinated to the Ag(I) ion via the triazole nitrogen atom forming a cationic [Ag(itraco-N)(2)]+ part, which is neutralized by the nitrate anion. The antifungal effect of silver(I) complex and itraconazole was evaluated against four different Candida species (C. albicans, C. glabrata, C. parapsilosis and C. krusei) by means of minimal inhibitory concentrations (MICs). Agitraco complex shows enhanced antifungal activity than itraco, being 2.3- and 4.5-fold more active against C. albicans and C. glabrata, respectively. The complex was also more efficient in inhibiting yeast to hyphae transition process in C. albicans, which is an important step in its pathogenesis. Part of the improved activity of Agitraco could be attributed to the greater induction of reactive oxygen species in Candida spp. with respect to itraco. The toxicity evaluation in the zebrafish model (Danio rerio) suggests that the Agitraco complex has better therapeutic profile and improved antifungal efficacy with respect to the parent drug, which were also proven in vivo using the zebrafish model of lethal disseminated candidiasis. Interaction of Agitraco with bovine serum albumin (BSA) was investigated with the aim to assess its binding affinity toward this biomolecule.
PB  - Elsevier, Amsterdam
T2  - Journal of Molecular Structure
T1  - Improvement of the anti-Candida activity of itraconazole in the zebrafish infection model by its coordination to silver(I)
VL  - 1232
DO  - 10.1016/j.molstruc.2021.130006
ER  - 
@article{
author = "Stevanović, Nevena Lj. and Glišić, Biljana and Vojnović, Sandra and Wadepohl, Hubert and Andrejević, Tina P. and Durić, Sonja Z. and Savić, Nada D. and Nikodinović-Runić, Jasmina and Djuran, Milos  and Pavić, Aleksandar",
year = "2021",
abstract = "In order to develop a novel antifungal agent, we synthesized and completely structurally characterized the silver(I) complex with the known antimycotic itraconazole (itraco), [Ag(itraco-N)(2)]NO3 center dot H2O (Agitraco). The spectroscopic and crystallographic results revealed that, in this complex, two itraco ligands are monodentately coordinated to the Ag(I) ion via the triazole nitrogen atom forming a cationic [Ag(itraco-N)(2)]+ part, which is neutralized by the nitrate anion. The antifungal effect of silver(I) complex and itraconazole was evaluated against four different Candida species (C. albicans, C. glabrata, C. parapsilosis and C. krusei) by means of minimal inhibitory concentrations (MICs). Agitraco complex shows enhanced antifungal activity than itraco, being 2.3- and 4.5-fold more active against C. albicans and C. glabrata, respectively. The complex was also more efficient in inhibiting yeast to hyphae transition process in C. albicans, which is an important step in its pathogenesis. Part of the improved activity of Agitraco could be attributed to the greater induction of reactive oxygen species in Candida spp. with respect to itraco. The toxicity evaluation in the zebrafish model (Danio rerio) suggests that the Agitraco complex has better therapeutic profile and improved antifungal efficacy with respect to the parent drug, which were also proven in vivo using the zebrafish model of lethal disseminated candidiasis. Interaction of Agitraco with bovine serum albumin (BSA) was investigated with the aim to assess its binding affinity toward this biomolecule.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Molecular Structure",
title = "Improvement of the anti-Candida activity of itraconazole in the zebrafish infection model by its coordination to silver(I)",
volume = "1232",
doi = "10.1016/j.molstruc.2021.130006"
}
Stevanović, N. Lj., Glišić, B., Vojnović, S., Wadepohl, H., Andrejević, T. P., Durić, S. Z., Savić, N. D., Nikodinović-Runić, J., Djuran, M.,& Pavić, A.. (2021). Improvement of the anti-Candida activity of itraconazole in the zebrafish infection model by its coordination to silver(I). in Journal of Molecular Structure
Elsevier, Amsterdam., 1232.
https://doi.org/10.1016/j.molstruc.2021.130006
Stevanović NL, Glišić B, Vojnović S, Wadepohl H, Andrejević TP, Durić SZ, Savić ND, Nikodinović-Runić J, Djuran M, Pavić A. Improvement of the anti-Candida activity of itraconazole in the zebrafish infection model by its coordination to silver(I). in Journal of Molecular Structure. 2021;1232.
doi:10.1016/j.molstruc.2021.130006 .
Stevanović, Nevena Lj., Glišić, Biljana, Vojnović, Sandra, Wadepohl, Hubert, Andrejević, Tina P., Durić, Sonja Z., Savić, Nada D., Nikodinović-Runić, Jasmina, Djuran, Milos , Pavić, Aleksandar, "Improvement of the anti-Candida activity of itraconazole in the zebrafish infection model by its coordination to silver(I)" in Journal of Molecular Structure, 1232 (2021),
https://doi.org/10.1016/j.molstruc.2021.130006 . .
10
10