Lazić, Jelena

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Authority KeyName Variants
orcid::0000-0003-2618-3573
  • Lazić, Jelena (22)
Projects
info:eu-repo/grantAgreement/MESTD/inst-2020/200042/RS// info:eu-repo/grantAgreement/ScienceFundRS/Ideje/7730810/RS//
The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors Microbial diversity study and characterization of beneficial environmental microorganisms
info:eu-repo/grantAgreement/MESTD/inst-2020/200122/RS// Deutscher Akademischer Austauschdienst e.V. (DAAD) [57381332]
Emmy-Noether program of the German Research Foundation [GU 1134/3] info:eu-repo/grantAgreement/MESTD/inst-2020/200378/RS//
Serbian Academy of Sciences and Arts under project No. F128 Bacterial biomolecules, PHA and PG, were successfully combined to produce film materials as potential sustainable and active food packaging material alternatives to conventional plastics. The incorporation of PG into the biopolymer matrix has improved the optical properties and antioxidative potential of the obtained films rendering them as suitable alternatives for packaging applications.
Centre for Research Infrastructure at the University of Ljubljana, Faculty of Chemistry and Chemical Technology, which is part of the Network of Research and Infrastructural Centres UL (MRIC UL) European Cooperation in Science and Technology (CA21145 - COST Action EURESTOP)
European Research Council [ERC-StG-678905 CoBABATI] European Society of Clinical Microbiology and Infectious Diseases (ESCMID)
European Union's Horizon 2020 research and innovation program under grant agreement No. 870292 FCT—Fundação para a Ciência e a Tecnologia, in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences—UCIBIO, project LA/P/0140/202019 of the Associate Laboratory Institute for Health and Bioeconomy—i4HB.
OPATHY - From Omics to Patient: Improving Diagnostics of Pathogenic Yeasts Design, synthesis and investigations of fullerene based nanomolecular machines
Allergens, antibodies, enzymes and small physiologically important molecules: design, structure, function and relevance info:eu-repo/grantAgreement/MESTD/inst-2020/200026/RS//
info:eu-repo/grantAgreement/ScienceFundRS/Ideje/7750288/RS// INSERM
Javna Agencija za Raziskovalno Dejavnost RS (I0-0022) Javna Agencija za Raziskovalno Dejavnost RS ( P1-0175)
Ministarstvo Prosvete, Nauke i Tehnološkog Razvoja - Bilateral project No. 19 between University of Kragujevac, Faculty of Science, Serbia and University of Ljubljana, Faculty of Chemistry and Chemical Technology, Ljubljana, Slovenia nfo:eu-repo/grantAgreement/MESTD/inst-2020/200122/RS//
PHC French-Serbian partnership project Pavle Savic [451-03-01963/2017-09/03] Science Fund of the Republic of Serbia, IDEJE [7730810]
Serbian Academy of Sciences and Arts Serbian Academy of Sciences and Arts (F128)

Author's Bibliography

Silver(I) complexes with voriconazole as promising anti-Candida agents

Stanković, Mia; Škaro Bogojević, Sanja; Kljun, Jakob; Milanović, Žiko; Stevanović, Nevena; Lazić, Jelena; Vojnović, Sandra; Turel, Iztok; Đuran, Miloš; Glišić, Biljana

(Elsevier, 2024)

TY  - JOUR
AU  - Stanković, Mia
AU  - Škaro Bogojević, Sanja
AU  - Kljun, Jakob
AU  - Milanović, Žiko
AU  - Stevanović, Nevena
AU  - Lazić, Jelena
AU  - Vojnović, Sandra
AU  - Turel, Iztok
AU  - Đuran, Miloš
AU  - Glišić, Biljana
PY  - 2024
UR  - https://www.sciencedirect.com/science/article/pii/S0162013424000953
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2368
AB  - Recognizing that metal ions play an important role in modifying the pharmacological properties of known organic-based drugs, the present manuscript addresses the complexation of the antifungal agent voriconazole (vcz) with the biologically relevant silver(I) ion as a strategy for the development of new antimycotics. The synthesized silver(I) complexes with vcz were characterized by mass spectrometry, IR, UV–Vis and NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystallographic results showed that complexes {[Ag(vcz)(H2O)]CH3SO3}n (1), {[Ag(vcz)2]BF4}n (2) and {[Ag(vcz)2]PF6}n (3) have polymeric structures in the solid state, in which silver(I) ions have a distorted tetrahedral geometry. On the other hand, DFT calculations revealed that the investigated silver(I) complexes 1–3 in DMSO exist as linear [Ag(vcz-N2)(vcz-N19)]+ (1a), [Ag(vcz-N2)(vcz-N4)]+ (2a) and [Ag(vcz-N4)2]+ (3a) species, respectively. The evaluated complexes showed an enhanced anti-Candida activity compared to the parent drug with minimal inhibitory concentration (MIC) values in the range of 0.02–1.05 μM. In comparison with vcz, the corresponding silver(I) complexes showed better activity in prevention hyphae and biofilm formation of C. albicans, indicating that they could be considered as promising agents against Candida that significantly inhibit its virulence. Also, these complexes are much better inhibitors of ergosterol synthesis in the cell membrane of C. albicans at the concentration of 0.5 × MIC. This is also confirmed by a molecular docking, which revealed that complexes 1a – 3a showed better inhibitory activity than vcz against the sterol 14α-demethylase enzyme cytochrome P450 (CYP51B), which plays a crucial role in the formation of ergosterol.
PB  - Elsevier
T2  - Journal of Inorganic Biochemistry
T1  - Silver(I) complexes with voriconazole as promising anti-Candida agents
SP  - 112572
VL  - 256
DO  - 10.1016/j.jinorgbio.2024.112572
ER  - 
@article{
author = "Stanković, Mia and Škaro Bogojević, Sanja and Kljun, Jakob and Milanović, Žiko and Stevanović, Nevena and Lazić, Jelena and Vojnović, Sandra and Turel, Iztok and Đuran, Miloš and Glišić, Biljana",
year = "2024",
abstract = "Recognizing that metal ions play an important role in modifying the pharmacological properties of known organic-based drugs, the present manuscript addresses the complexation of the antifungal agent voriconazole (vcz) with the biologically relevant silver(I) ion as a strategy for the development of new antimycotics. The synthesized silver(I) complexes with vcz were characterized by mass spectrometry, IR, UV–Vis and NMR spectroscopy and single-crystal X-ray diffraction analysis. The crystallographic results showed that complexes {[Ag(vcz)(H2O)]CH3SO3}n (1), {[Ag(vcz)2]BF4}n (2) and {[Ag(vcz)2]PF6}n (3) have polymeric structures in the solid state, in which silver(I) ions have a distorted tetrahedral geometry. On the other hand, DFT calculations revealed that the investigated silver(I) complexes 1–3 in DMSO exist as linear [Ag(vcz-N2)(vcz-N19)]+ (1a), [Ag(vcz-N2)(vcz-N4)]+ (2a) and [Ag(vcz-N4)2]+ (3a) species, respectively. The evaluated complexes showed an enhanced anti-Candida activity compared to the parent drug with minimal inhibitory concentration (MIC) values in the range of 0.02–1.05 μM. In comparison with vcz, the corresponding silver(I) complexes showed better activity in prevention hyphae and biofilm formation of C. albicans, indicating that they could be considered as promising agents against Candida that significantly inhibit its virulence. Also, these complexes are much better inhibitors of ergosterol synthesis in the cell membrane of C. albicans at the concentration of 0.5 × MIC. This is also confirmed by a molecular docking, which revealed that complexes 1a – 3a showed better inhibitory activity than vcz against the sterol 14α-demethylase enzyme cytochrome P450 (CYP51B), which plays a crucial role in the formation of ergosterol.",
publisher = "Elsevier",
journal = "Journal of Inorganic Biochemistry",
title = "Silver(I) complexes with voriconazole as promising anti-Candida agents",
pages = "112572",
volume = "256",
doi = "10.1016/j.jinorgbio.2024.112572"
}
Stanković, M., Škaro Bogojević, S., Kljun, J., Milanović, Ž., Stevanović, N., Lazić, J., Vojnović, S., Turel, I., Đuran, M.,& Glišić, B.. (2024). Silver(I) complexes with voriconazole as promising anti-Candida agents. in Journal of Inorganic Biochemistry
Elsevier., 256, 112572.
https://doi.org/10.1016/j.jinorgbio.2024.112572
Stanković M, Škaro Bogojević S, Kljun J, Milanović Ž, Stevanović N, Lazić J, Vojnović S, Turel I, Đuran M, Glišić B. Silver(I) complexes with voriconazole as promising anti-Candida agents. in Journal of Inorganic Biochemistry. 2024;256:112572.
doi:10.1016/j.jinorgbio.2024.112572 .
Stanković, Mia, Škaro Bogojević, Sanja, Kljun, Jakob, Milanović, Žiko, Stevanović, Nevena, Lazić, Jelena, Vojnović, Sandra, Turel, Iztok, Đuran, Miloš, Glišić, Biljana, "Silver(I) complexes with voriconazole as promising anti-Candida agents" in Journal of Inorganic Biochemistry, 256 (2024):112572,
https://doi.org/10.1016/j.jinorgbio.2024.112572 . .
3

Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion

Stanković, Mia; Kljun, Jakob; Stevanović, Nevena Lj.; Lazić, Jelena; Škaro Bogojević, Sanja; Vojnović, Sandra; Zlatar, Matija; Nikodinović-Runić, Jasmina; Turel, Iztok; Đuran, Miloš; Glišić, Biljana

(Royal Society of Chemistry (RSC), 2024)

TY  - JOUR
AU  - Stanković, Mia
AU  - Kljun, Jakob
AU  - Stevanović, Nevena Lj.
AU  - Lazić, Jelena
AU  - Škaro Bogojević, Sanja
AU  - Vojnović, Sandra
AU  - Zlatar, Matija
AU  - Nikodinović-Runić, Jasmina
AU  - Turel, Iztok
AU  - Đuran, Miloš
AU  - Glišić, Biljana
PY  - 2024
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2303
AB  - Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)2]SbF6 (1, ecz is econazole), {[Ag(vcz)2]SbF6}n (2, vcz is voriconazole), and [Ag(ctz)2]SbF6 (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and 1H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01–27.1 and 2.61–47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1–3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against Candida glabrata with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of C. albicans hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on Candida pathogenesis, its effect on the adherence of C. albicans to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied.
PB  - Royal Society of Chemistry (RSC)
T2  - Dalton Transactions
T1  - Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion
DO  - 10.1039/D3DT03010E
ER  - 
@article{
author = "Stanković, Mia and Kljun, Jakob and Stevanović, Nevena Lj. and Lazić, Jelena and Škaro Bogojević, Sanja and Vojnović, Sandra and Zlatar, Matija and Nikodinović-Runić, Jasmina and Turel, Iztok and Đuran, Miloš and Glišić, Biljana",
year = "2024",
abstract = "Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)2]SbF6 (1, ecz is econazole), {[Ag(vcz)2]SbF6}n (2, vcz is voriconazole), and [Ag(ctz)2]SbF6 (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and 1H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01–27.1 and 2.61–47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1–3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against Candida glabrata with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of C. albicans hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on Candida pathogenesis, its effect on the adherence of C. albicans to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied.",
publisher = "Royal Society of Chemistry (RSC)",
journal = "Dalton Transactions",
title = "Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion",
doi = "10.1039/D3DT03010E"
}
Stanković, M., Kljun, J., Stevanović, N. Lj., Lazić, J., Škaro Bogojević, S., Vojnović, S., Zlatar, M., Nikodinović-Runić, J., Turel, I., Đuran, M.,& Glišić, B.. (2024). Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion. in Dalton Transactions
Royal Society of Chemistry (RSC)..
https://doi.org/10.1039/D3DT03010E
Stanković M, Kljun J, Stevanović NL, Lazić J, Škaro Bogojević S, Vojnović S, Zlatar M, Nikodinović-Runić J, Turel I, Đuran M, Glišić B. Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion. in Dalton Transactions. 2024;.
doi:10.1039/D3DT03010E .
Stanković, Mia, Kljun, Jakob, Stevanović, Nevena Lj., Lazić, Jelena, Škaro Bogojević, Sanja, Vojnović, Sandra, Zlatar, Matija, Nikodinović-Runić, Jasmina, Turel, Iztok, Đuran, Miloš, Glišić, Biljana, "Silver(I) complexes containing antifungal azoles: significant improvement of the anti-Candida potential of the azole drug after its coordination to the silver(I) ion" in Dalton Transactions (2024),
https://doi.org/10.1039/D3DT03010E . .
4
1

Late-stage diversification of bacterial natural products through biocatalysis

Lazić, Jelena; Filipović, Vuk; Pantelić, Lena; Milovanović, Jelena; Vojnović, Sandra; Nikodinović-Runić, Jasmina

(Frontiers, 2024)

TY  - JOUR
AU  - Lazić, Jelena
AU  - Filipović, Vuk
AU  - Pantelić, Lena
AU  - Milovanović, Jelena
AU  - Vojnović, Sandra
AU  - Nikodinović-Runić, Jasmina
PY  - 2024
UR  - https://www.frontiersin.org/articles/10.3389/fbioe.2024.1351583
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2387
AB  - Bacterial natural products (BNPs) have been and still are very important sources of leads for drug development and chemical novelty. The possibility to perform late-stage diversification of these biomolecules is an attractive approach to obtain novel structures by means other than total chemical synthesis or metal complexation reactions. Although biocatalysis is gaining popularity within the context of green chemistry, a vast majority of the sequenced genome data aimed at deciphering metabolic pathways for BNP biosynthesis, possibly containing additional tailoring enzymes, remains underexplored. In this review, we report a systematic overview of biotransformations of 21 molecules, which include derivatization by halogenation, esterification, reduction, oxidation, alkylation and nitration reactions, as well as degradation products as their sub-derivatives. These BNPs were grouped based on their biological activities into antibacterial (5), antifungal (5), anticancer (5), immunosuppressive (2) and quorum sensing modulating (4) compounds. This study summarized 73 derivatives and 16 degradation sub-derivatives originating from 12 BNPs. The remaining 9 BNPs have not been reported as substrates in biotransformation reactions. The highest number of 28 biocatalytic reactions was reported for the antibacterial drug vancomycin, followed by 18 reactions reported for the immunosuppressive drug rapamycin, suggesting that research focus to date was more on BNPs that were already in clinical use. The most common biocatalysts include oxidoreductases, transferases, lipases, isomerases and haloperoxidases. This review highlights biocatalytic routes for the late-stage diversification reactions of BNPs, which potentially help to recognize the structural optimizations of bioactive scaffolds for the generation of new biomolecules, eventually leading to drug development.
PB  - Frontiers
T2  - Frontiers in Bioengineering and Biotechnology
T1  - Late-stage diversification of bacterial natural products through biocatalysis
VL  - 12
DO  - 10.3389/fbioe.2024.1351583
ER  - 
@article{
author = "Lazić, Jelena and Filipović, Vuk and Pantelić, Lena and Milovanović, Jelena and Vojnović, Sandra and Nikodinović-Runić, Jasmina",
year = "2024",
abstract = "Bacterial natural products (BNPs) have been and still are very important sources of leads for drug development and chemical novelty. The possibility to perform late-stage diversification of these biomolecules is an attractive approach to obtain novel structures by means other than total chemical synthesis or metal complexation reactions. Although biocatalysis is gaining popularity within the context of green chemistry, a vast majority of the sequenced genome data aimed at deciphering metabolic pathways for BNP biosynthesis, possibly containing additional tailoring enzymes, remains underexplored. In this review, we report a systematic overview of biotransformations of 21 molecules, which include derivatization by halogenation, esterification, reduction, oxidation, alkylation and nitration reactions, as well as degradation products as their sub-derivatives. These BNPs were grouped based on their biological activities into antibacterial (5), antifungal (5), anticancer (5), immunosuppressive (2) and quorum sensing modulating (4) compounds. This study summarized 73 derivatives and 16 degradation sub-derivatives originating from 12 BNPs. The remaining 9 BNPs have not been reported as substrates in biotransformation reactions. The highest number of 28 biocatalytic reactions was reported for the antibacterial drug vancomycin, followed by 18 reactions reported for the immunosuppressive drug rapamycin, suggesting that research focus to date was more on BNPs that were already in clinical use. The most common biocatalysts include oxidoreductases, transferases, lipases, isomerases and haloperoxidases. This review highlights biocatalytic routes for the late-stage diversification reactions of BNPs, which potentially help to recognize the structural optimizations of bioactive scaffolds for the generation of new biomolecules, eventually leading to drug development.",
publisher = "Frontiers",
journal = "Frontiers in Bioengineering and Biotechnology",
title = "Late-stage diversification of bacterial natural products through biocatalysis",
volume = "12",
doi = "10.3389/fbioe.2024.1351583"
}
Lazić, J., Filipović, V., Pantelić, L., Milovanović, J., Vojnović, S.,& Nikodinović-Runić, J.. (2024). Late-stage diversification of bacterial natural products through biocatalysis. in Frontiers in Bioengineering and Biotechnology
Frontiers., 12.
https://doi.org/10.3389/fbioe.2024.1351583
Lazić J, Filipović V, Pantelić L, Milovanović J, Vojnović S, Nikodinović-Runić J. Late-stage diversification of bacterial natural products through biocatalysis. in Frontiers in Bioengineering and Biotechnology. 2024;12.
doi:10.3389/fbioe.2024.1351583 .
Lazić, Jelena, Filipović, Vuk, Pantelić, Lena, Milovanović, Jelena, Vojnović, Sandra, Nikodinović-Runić, Jasmina, "Late-stage diversification of bacterial natural products through biocatalysis" in Frontiers in Bioengineering and Biotechnology, 12 (2024),
https://doi.org/10.3389/fbioe.2024.1351583 . .
1

Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin

Ponjavić, Marijana; Malagurski, Ivana; Lazić, Jelena; Jeremić, Sanja; Pavlović, Vladimir; Prlainović, Nevena; Maksimović, Vesna; Cosović, Vladan; Atanase, Leonard Ionut; Freitas, Filomena; Matos, Mariana; Nikodinović-Runić, Jasmina

(2023)

TY  - JOUR
AU  - Ponjavić, Marijana
AU  - Malagurski, Ivana
AU  - Lazić, Jelena
AU  - Jeremić, Sanja
AU  - Pavlović, Vladimir
AU  - Prlainović, Nevena
AU  - Maksimović, Vesna
AU  - Cosović, Vladan
AU  - Atanase, Leonard Ionut
AU  - Freitas, Filomena
AU  - Matos, Mariana
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1714
AB  - The quest for sustainable biomaterials with excellent biocompatibility and tailorable properties has put polyhydroxyalkanoates (PHAs) into the research spotlight. However, high production costs and the lack of bioactivity limit their market penetration. To address this, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was combined with a bacterial pigment with strong anticancer activity, prodigiosin (PG), to obtain functionally enhanced PHBV-based biomaterials. The samples were produced in the form of films 115.6–118.8 µm in thickness using the solvent casting method. The effects of PG incorporation on the physical properties (morphology, biopolymer crystallinity and thermal stability) and functionality of the obtained biomaterials were investigated. PG has acted as a nucleating agent, in turn affecting the degree of crystallinity, thermal stability and morphology of the films. All samples with PG had a more organized internal structure and higher melting and degradation temperatures. The calculated degree of crystallinity of the PHBV copolymer was 53%, while the PG1, PG3 and PG3 films had values of 64.0%, 63.9% and 69.2%, respectively. Cytotoxicity studies have shown the excellent anticancer activity of films against HCT116 (colon cancer) cells, thus advancing PHBV biomedical application potential.
T2  - International Journal of Molecular Sciences
T2  - International Journal of Molecular Sciences
T1  - Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin
IS  - 3
SP  - 1906
VL  - 24
DO  - 10.3390/ijms24031906
ER  - 
@article{
author = "Ponjavić, Marijana and Malagurski, Ivana and Lazić, Jelena and Jeremić, Sanja and Pavlović, Vladimir and Prlainović, Nevena and Maksimović, Vesna and Cosović, Vladan and Atanase, Leonard Ionut and Freitas, Filomena and Matos, Mariana and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "The quest for sustainable biomaterials with excellent biocompatibility and tailorable properties has put polyhydroxyalkanoates (PHAs) into the research spotlight. However, high production costs and the lack of bioactivity limit their market penetration. To address this, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) was combined with a bacterial pigment with strong anticancer activity, prodigiosin (PG), to obtain functionally enhanced PHBV-based biomaterials. The samples were produced in the form of films 115.6–118.8 µm in thickness using the solvent casting method. The effects of PG incorporation on the physical properties (morphology, biopolymer crystallinity and thermal stability) and functionality of the obtained biomaterials were investigated. PG has acted as a nucleating agent, in turn affecting the degree of crystallinity, thermal stability and morphology of the films. All samples with PG had a more organized internal structure and higher melting and degradation temperatures. The calculated degree of crystallinity of the PHBV copolymer was 53%, while the PG1, PG3 and PG3 films had values of 64.0%, 63.9% and 69.2%, respectively. Cytotoxicity studies have shown the excellent anticancer activity of films against HCT116 (colon cancer) cells, thus advancing PHBV biomedical application potential.",
journal = "International Journal of Molecular Sciences, International Journal of Molecular Sciences",
title = "Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin",
number = "3",
pages = "1906",
volume = "24",
doi = "10.3390/ijms24031906"
}
Ponjavić, M., Malagurski, I., Lazić, J., Jeremić, S., Pavlović, V., Prlainović, N., Maksimović, V., Cosović, V., Atanase, L. I., Freitas, F., Matos, M.,& Nikodinović-Runić, J.. (2023). Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin. in International Journal of Molecular Sciences, 24(3), 1906.
https://doi.org/10.3390/ijms24031906
Ponjavić M, Malagurski I, Lazić J, Jeremić S, Pavlović V, Prlainović N, Maksimović V, Cosović V, Atanase LI, Freitas F, Matos M, Nikodinović-Runić J. Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin. in International Journal of Molecular Sciences. 2023;24(3):1906.
doi:10.3390/ijms24031906 .
Ponjavić, Marijana, Malagurski, Ivana, Lazić, Jelena, Jeremić, Sanja, Pavlović, Vladimir, Prlainović, Nevena, Maksimović, Vesna, Cosović, Vladan, Atanase, Leonard Ionut, Freitas, Filomena, Matos, Mariana, Nikodinović-Runić, Jasmina, "Advancing PHBV Biomedical Potential with the Incorporation of Bacterial Biopigment Prodigiosin" in International Journal of Molecular Sciences, 24, no. 3 (2023):1906,
https://doi.org/10.3390/ijms24031906 . .
2
10

From waste streams to biotherapeutics: making a connection using bacteria

Lazić, Jelena; Nikodinović-Runić, Jasmina

(Belgrade : Serbian Chemical Society and Serbian Young Chemists’ Club, 2023)

TY  - CONF
AU  - Lazić, Jelena
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://www.chem.bg.ac.rs/pz/news1.py?q=3820&l=1
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2205
AB  - Microorganisms, our planet’s original inhabitants discovered with the invention of the
first microscope in the 17th century, have consistently facilitated our daily life. However,
our modern life generates enormous amounts of wastes, such as plastic, food, and
chemicals from the pharmaceutical industry. Bacterial natural products hold an
important position in this industry, as drug leads in synthetic chemistry and biology,
essential for the discovery of effective agents against a variety of human diseases. If the
existing waste is used as a nutrient source for microbial production of valuable
biomolecules, that concept is called “waste to value” or “upcycling”.
This concept was explored using bacterial biopigment prodigiosin (PG, Fig. 1) as part of
the BioECOLogics project. This proof of concept demonstrates how the bacteria Serratia
marcescens ATCC 27117 can use a waste stream from the food industry as a carbon
source to grow and produce its bioactive secondary metabolite PG. The unique structure
of this molecule was changed through green chemical [1] and biopolymer formulation
[2] approaches, as well as metal complexation. Finally, these sustainable biotherapeutics
were validated in vitro (antimicrobial, anticancer) and in vivo (nematode Caenorhabditis
elegans and zebrafish Danio rerio).
PB  - Belgrade : Serbian Chemical Society and Serbian Young Chemists’ Club
C3  - 9th Conference of Young Chemists of Serbia
T1  - From waste streams to biotherapeutics: making a connection using bacteria
EP  - 6
SP  - 6
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2205
ER  - 
@conference{
author = "Lazić, Jelena and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "Microorganisms, our planet’s original inhabitants discovered with the invention of the
first microscope in the 17th century, have consistently facilitated our daily life. However,
our modern life generates enormous amounts of wastes, such as plastic, food, and
chemicals from the pharmaceutical industry. Bacterial natural products hold an
important position in this industry, as drug leads in synthetic chemistry and biology,
essential for the discovery of effective agents against a variety of human diseases. If the
existing waste is used as a nutrient source for microbial production of valuable
biomolecules, that concept is called “waste to value” or “upcycling”.
This concept was explored using bacterial biopigment prodigiosin (PG, Fig. 1) as part of
the BioECOLogics project. This proof of concept demonstrates how the bacteria Serratia
marcescens ATCC 27117 can use a waste stream from the food industry as a carbon
source to grow and produce its bioactive secondary metabolite PG. The unique structure
of this molecule was changed through green chemical [1] and biopolymer formulation
[2] approaches, as well as metal complexation. Finally, these sustainable biotherapeutics
were validated in vitro (antimicrobial, anticancer) and in vivo (nematode Caenorhabditis
elegans and zebrafish Danio rerio).",
publisher = "Belgrade : Serbian Chemical Society and Serbian Young Chemists’ Club",
journal = "9th Conference of Young Chemists of Serbia",
title = "From waste streams to biotherapeutics: making a connection using bacteria",
pages = "6-6",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2205"
}
Lazić, J.,& Nikodinović-Runić, J.. (2023). From waste streams to biotherapeutics: making a connection using bacteria. in 9th Conference of Young Chemists of Serbia
Belgrade : Serbian Chemical Society and Serbian Young Chemists’ Club., 6-6.
https://hdl.handle.net/21.15107/rcub_imagine_2205
Lazić J, Nikodinović-Runić J. From waste streams to biotherapeutics: making a connection using bacteria. in 9th Conference of Young Chemists of Serbia. 2023;:6-6.
https://hdl.handle.net/21.15107/rcub_imagine_2205 .
Lazić, Jelena, Nikodinović-Runić, Jasmina, "From waste streams to biotherapeutics: making a connection using bacteria" in 9th Conference of Young Chemists of Serbia (2023):6-6,
https://hdl.handle.net/21.15107/rcub_imagine_2205 .

Medium chain length polyhyoxyalkanoates (mcl-PHA) model compounds for the discovery of novel PHA depolymerases

Nenadović, Marija; Pantelić, Brana; Lazić, Jelena; Maslak, Veselin; Nikodinović-Runić, Jasmina; Milovanović, Jelena

(2023)

TY  - CONF
AU  - Nenadović, Marija
AU  - Pantelić, Brana
AU  - Lazić, Jelena
AU  - Maslak, Veselin
AU  - Nikodinović-Runić, Jasmina
AU  - Milovanović, Jelena
PY  - 2023
UR  - https://afea.eventsair.com/10th-conference-of-mikrobiokosmos/abstract-book
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2237
AB  - PHAs are naturally made microbial polyesters that
have been commercialized as biodegradable
plastics. However, it has been shown that these
materials are not so easily biodegraded in natural
environments [1]. PHA depolymerases are key PHA
degrading enzymes and their identification and
characterization is of great interest and importance.
Currently, screening is done on polymeric
substrates using techniques such as clear zone
assays on agar or weight loss measurements.
Results obtained using these different methods
cannot be directly compared, since they depend
highly on the polymer used, PHA granules
preparation and assay conditions [2].
In order to design a more specific test for the
determination of PHA depolymerase activity, we
synthesized 3-hyoxyalkanoate monomers (3-HA
monomer) and 3-hyoxyalkanoic acid dimers (3-HA
dimer) and their respective p-nitrophenyl esters,
allowing for spectrophotometric determination of
their activity [3]. Compounds were characterized
using N and FTIR. Para-nitrophenyl labeled
substrates were then used in the enzymatic activity
assay with the benchmark polyhyoxyoctanoate
(PHO) depolymerase from Pseudomonas
fluorescens GK13 expressed in Escherichia coli
CodonPlus-RIPL hosts. This activity was compared
to recombinantly expressed leaf-branch compost
cutinase (LCC cutinase) and
polyethyleneterephtalate (PET) hyolyzing esterase
from Ideonella sakaiensis (IsPETase). Our initial
results revealed increased specificity of PHO
depolymerase towards newly synthetized
substrates, suggesting their suitability for specific
screens and isolation of new mcl-PHA
depolymerases, as well as in high throughput
screening assays designed for guiding their
directed evolution.
C3  - 10th Conference of Mikrobiokosmos
T1  - Medium chain length polyhyoxyalkanoates (mcl-PHA) model compounds for the discovery of novel PHA depolymerases
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2237
ER  - 
@conference{
author = "Nenadović, Marija and Pantelić, Brana and Lazić, Jelena and Maslak, Veselin and Nikodinović-Runić, Jasmina and Milovanović, Jelena",
year = "2023",
abstract = "PHAs are naturally made microbial polyesters that
have been commercialized as biodegradable
plastics. However, it has been shown that these
materials are not so easily biodegraded in natural
environments [1]. PHA depolymerases are key PHA
degrading enzymes and their identification and
characterization is of great interest and importance.
Currently, screening is done on polymeric
substrates using techniques such as clear zone
assays on agar or weight loss measurements.
Results obtained using these different methods
cannot be directly compared, since they depend
highly on the polymer used, PHA granules
preparation and assay conditions [2].
In order to design a more specific test for the
determination of PHA depolymerase activity, we
synthesized 3-hyoxyalkanoate monomers (3-HA
monomer) and 3-hyoxyalkanoic acid dimers (3-HA
dimer) and their respective p-nitrophenyl esters,
allowing for spectrophotometric determination of
their activity [3]. Compounds were characterized
using N and FTIR. Para-nitrophenyl labeled
substrates were then used in the enzymatic activity
assay with the benchmark polyhyoxyoctanoate
(PHO) depolymerase from Pseudomonas
fluorescens GK13 expressed in Escherichia coli
CodonPlus-RIPL hosts. This activity was compared
to recombinantly expressed leaf-branch compost
cutinase (LCC cutinase) and
polyethyleneterephtalate (PET) hyolyzing esterase
from Ideonella sakaiensis (IsPETase). Our initial
results revealed increased specificity of PHO
depolymerase towards newly synthetized
substrates, suggesting their suitability for specific
screens and isolation of new mcl-PHA
depolymerases, as well as in high throughput
screening assays designed for guiding their
directed evolution.",
journal = "10th Conference of Mikrobiokosmos",
title = "Medium chain length polyhyoxyalkanoates (mcl-PHA) model compounds for the discovery of novel PHA depolymerases",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2237"
}
Nenadović, M., Pantelić, B., Lazić, J., Maslak, V., Nikodinović-Runić, J.,& Milovanović, J.. (2023). Medium chain length polyhyoxyalkanoates (mcl-PHA) model compounds for the discovery of novel PHA depolymerases. in 10th Conference of Mikrobiokosmos.
https://hdl.handle.net/21.15107/rcub_imagine_2237
Nenadović M, Pantelić B, Lazić J, Maslak V, Nikodinović-Runić J, Milovanović J. Medium chain length polyhyoxyalkanoates (mcl-PHA) model compounds for the discovery of novel PHA depolymerases. in 10th Conference of Mikrobiokosmos. 2023;.
https://hdl.handle.net/21.15107/rcub_imagine_2237 .
Nenadović, Marija, Pantelić, Brana, Lazić, Jelena, Maslak, Veselin, Nikodinović-Runić, Jasmina, Milovanović, Jelena, "Medium chain length polyhyoxyalkanoates (mcl-PHA) model compounds for the discovery of novel PHA depolymerases" in 10th Conference of Mikrobiokosmos (2023),
https://hdl.handle.net/21.15107/rcub_imagine_2237 .

DNA/BSA interactions and biological activity of prodigiosin and its copper(II) complex

Glišić, Biljana; Andrejević, Tina; Lazić, Jelena; Ilić-Tomić, Tatjana; Ašanin, Darko; Pantović, Bojana; Djuran, Miloš; Nikodinović-Runić, Jasmina

(Greece : University of Ioannina, 2023)

TY  - CONF
AU  - Glišić, Biljana
AU  - Andrejević, Tina
AU  - Lazić, Jelena
AU  - Ilić-Tomić, Tatjana
AU  - Ašanin, Darko
AU  - Pantović, Bojana
AU  - Djuran, Miloš
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://isabc2023.com/
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1926
AB  - Prodigiosin (PG) is a red biopigment produced as a secondary metabolite by
microorganisms such as Serratia marcescens and Streptomyces. In recent years, this tripyrrole
compound has attracted an increasing attention due to its antibacterial, antimalarial, and
immunosuppressive activities [1]. It is also known for its antitumor activity, inducing the cell
death by apoptosis in different human cancer cell lines [2]. Considering this, in the present
study, we investigated the interactions of prodigiosin and its copper(II) complex (CuPG; the
structural formula is presented below), whose crystal structure was determined previously [2],
with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) by fluorescence emission
spectroscopy to clarify their binding affinities toward these biomolecules. The antimicrobial
activity of the synthesized CuPG complex and PG ligand was evaluated in vitro against various
microorganisms that can lead to many infections. Moreover, CuPG and PG were evaluated in
a cell viability assay on a healthy MRC-5 cell line, as well as a panel of MDA-MB-231, A549,
A375, and HCT116 cancer cell lines.
PB  - Greece : University of Ioannina
C3  - 16th International Symposium on Applied Bioinorganic Chemistry
T1  - DNA/BSA interactions and biological activity of prodigiosin and its
copper(II) complex
SP  - 264
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1926
ER  - 
@conference{
author = "Glišić, Biljana and Andrejević, Tina and Lazić, Jelena and Ilić-Tomić, Tatjana and Ašanin, Darko and Pantović, Bojana and Djuran, Miloš and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "Prodigiosin (PG) is a red biopigment produced as a secondary metabolite by
microorganisms such as Serratia marcescens and Streptomyces. In recent years, this tripyrrole
compound has attracted an increasing attention due to its antibacterial, antimalarial, and
immunosuppressive activities [1]. It is also known for its antitumor activity, inducing the cell
death by apoptosis in different human cancer cell lines [2]. Considering this, in the present
study, we investigated the interactions of prodigiosin and its copper(II) complex (CuPG; the
structural formula is presented below), whose crystal structure was determined previously [2],
with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) by fluorescence emission
spectroscopy to clarify their binding affinities toward these biomolecules. The antimicrobial
activity of the synthesized CuPG complex and PG ligand was evaluated in vitro against various
microorganisms that can lead to many infections. Moreover, CuPG and PG were evaluated in
a cell viability assay on a healthy MRC-5 cell line, as well as a panel of MDA-MB-231, A549,
A375, and HCT116 cancer cell lines.",
publisher = "Greece : University of Ioannina",
journal = "16th International Symposium on Applied Bioinorganic Chemistry",
title = "DNA/BSA interactions and biological activity of prodigiosin and its
copper(II) complex",
pages = "264",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1926"
}
Glišić, B., Andrejević, T., Lazić, J., Ilić-Tomić, T., Ašanin, D., Pantović, B., Djuran, M.,& Nikodinović-Runić, J.. (2023). DNA/BSA interactions and biological activity of prodigiosin and its
copper(II) complex. in 16th International Symposium on Applied Bioinorganic Chemistry
Greece : University of Ioannina., 264.
https://hdl.handle.net/21.15107/rcub_imagine_1926
Glišić B, Andrejević T, Lazić J, Ilić-Tomić T, Ašanin D, Pantović B, Djuran M, Nikodinović-Runić J. DNA/BSA interactions and biological activity of prodigiosin and its
copper(II) complex. in 16th International Symposium on Applied Bioinorganic Chemistry. 2023;:264.
https://hdl.handle.net/21.15107/rcub_imagine_1926 .
Glišić, Biljana, Andrejević, Tina, Lazić, Jelena, Ilić-Tomić, Tatjana, Ašanin, Darko, Pantović, Bojana, Djuran, Miloš, Nikodinović-Runić, Jasmina, "DNA/BSA interactions and biological activity of prodigiosin and its
copper(II) complex" in 16th International Symposium on Applied Bioinorganic Chemistry (2023):264,
https://hdl.handle.net/21.15107/rcub_imagine_1926 .

UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin

Ponjavić, Marijana; Malagurski, Ivana; Salevic-Jelic, Ana; Lazić, Jelena; Nikodinović-Runić, Jasmina

(Kragujevac : Institute for Information Technologies, 2023)

TY  - CONF
AU  - Ponjavić, Marijana
AU  - Malagurski, Ivana
AU  - Salevic-Jelic, Ana
AU  - Lazić, Jelena
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2106
AB  - New film materials based on bacterial biomolecules polyhydroxyalkanoate (poly(3-
hydroxybutyrate-co-3-hydroxyvalerate) PHBV) and prodigiosin (PG) were produced by
solvent casting as a potential food packaging material. Film precursors were obtained in a
sustainable manner via microbial fermentation using waste stream-based substrates (cooking oil
and second-grade canned meat, after the expiry date). The incorporation of PG into the PHBV has
influenced the morphology and functionality of the obtained materials. PG acted as a nucleating
agent, affecting in turn PHBV/PG film surface morphology. The films were intensively colored,
transparent and blocked UV-light. An increase in PG content decreased film transparency but it
did not affect UV-blocking ability. Migration experiments have shown that films possess the
potential to release PG into lipophilic food simulant media where it has exhibited antioxidative
action. The obtained results suggest that PHBV/PG films can be potentially used as sustainable
and active food packaging materials.
PB  - Kragujevac : Institute for Information Technologies
C3  - 2nd International Conference on Chemo and Bioinformatics
T1  - UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin
EP  - 1354
SP  - 1351
DO  - 10.46793/ICCBI23.351P
ER  - 
@conference{
author = "Ponjavić, Marijana and Malagurski, Ivana and Salevic-Jelic, Ana and Lazić, Jelena and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "New film materials based on bacterial biomolecules polyhydroxyalkanoate (poly(3-
hydroxybutyrate-co-3-hydroxyvalerate) PHBV) and prodigiosin (PG) were produced by
solvent casting as a potential food packaging material. Film precursors were obtained in a
sustainable manner via microbial fermentation using waste stream-based substrates (cooking oil
and second-grade canned meat, after the expiry date). The incorporation of PG into the PHBV has
influenced the morphology and functionality of the obtained materials. PG acted as a nucleating
agent, affecting in turn PHBV/PG film surface morphology. The films were intensively colored,
transparent and blocked UV-light. An increase in PG content decreased film transparency but it
did not affect UV-blocking ability. Migration experiments have shown that films possess the
potential to release PG into lipophilic food simulant media where it has exhibited antioxidative
action. The obtained results suggest that PHBV/PG films can be potentially used as sustainable
and active food packaging materials.",
publisher = "Kragujevac : Institute for Information Technologies",
journal = "2nd International Conference on Chemo and Bioinformatics",
title = "UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin",
pages = "1354-1351",
doi = "10.46793/ICCBI23.351P"
}
Ponjavić, M., Malagurski, I., Salevic-Jelic, A., Lazić, J.,& Nikodinović-Runić, J.. (2023). UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin. in 2nd International Conference on Chemo and Bioinformatics
Kragujevac : Institute for Information Technologies., 1351-1354.
https://doi.org/10.46793/ICCBI23.351P
Ponjavić M, Malagurski I, Salevic-Jelic A, Lazić J, Nikodinović-Runić J. UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin. in 2nd International Conference on Chemo and Bioinformatics. 2023;:1351-1354.
doi:10.46793/ICCBI23.351P .
Ponjavić, Marijana, Malagurski, Ivana, Salevic-Jelic, Ana, Lazić, Jelena, Nikodinović-Runić, Jasmina, "UV-blocking sustainable food packaging based on polyhydroxyalkanoate and bacterial pigment prodigiosin" in 2nd International Conference on Chemo and Bioinformatics (2023):1351-1354,
https://doi.org/10.46793/ICCBI23.351P . .

Biotechnological production of bacterial pigment prodigiosin and bioactive properties of its metal complexes with Cu(II) and Zn(II)

Lazić, Jelena; Milovanović, Jelena; Anejević, Tina; Ašanin, Darko; Ilić-Tomić, Tatjana; Glišić, Biljana; Nikodinović-Runić, Jasmina

(2023)

TY  - CONF
AU  - Lazić, Jelena
AU  - Milovanović, Jelena
AU  - Anejević, Tina
AU  - Ašanin, Darko
AU  - Ilić-Tomić, Tatjana
AU  - Glišić, Biljana
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://afea.eventsair.com/10th-conference-of-mikrobiokosmos/abstract-book
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2235
AB  - Prodigiosin (PG, Fig. 1a) is a biologically active
pyrrolylpyrromethene alkaloid whose structure was
first confirmed in 1962 [1]. PG is commonly
produced by Gram-negative bacteria, such as
Serratia spp. and has an eco-physiological role [2].
Its biological activities were extensively researched,
and numerous pharmacological properties were
established, including anticancer and
immunosuppressive However, high cost of extraction and purification
still represent the bottleneck in the microbial
production of PG. Meat and fish processing wastes have high potential as raw materials for conversion
into useful products of higher value. In this study,
meat offcuts were assessed as the sole nutrient for
the fermentative production of PG from S.
marcescens. Using this substrate lowered the
cultivation medium cost and shortened the
fermentation time to 12 h, while allowing a
satisfying PG yield of 83.1 mg/L. The isolated PG
was used in one-step reactions with CuCl₂ or ZnCl₂
in terc-BuOH at 25 °C. The obtained [Cu(PG)Cl] (Fig.
1b) and [Zn(PG)₂] (Fig. 1c) complexes were
characterized by UV-Vis and IR spectroscopy and
their bioactivity potential was assessed.
Antimicrobial activity was assessed in a disc assay
against 4 human pathogens: Escherichia coli NCTC
9001, Pseudomonas aeruginosa ATCC 10332,
Staphylococcus aureus NCTC 6571, Candida
albicans ATCC 10231, but no effect was observed
for the tested concentrations of 200 μg per disc and
lower. However, the anticancer potential of the new
derivatives is promising and the bovine serum
albumin (BSA) binding study revealed that
complexes bind to BSA tightly and reversibly [4].
C3  - 10th Conference of Mikrobiokosmos
T1  - Biotechnological production of bacterial pigment prodigiosin and bioactive properties of its metal complexes with Cu(II) and Zn(II)
UR  - https://hdl.handle.net/21.15107/rcub_imagine_2235
ER  - 
@conference{
author = "Lazić, Jelena and Milovanović, Jelena and Anejević, Tina and Ašanin, Darko and Ilić-Tomić, Tatjana and Glišić, Biljana and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "Prodigiosin (PG, Fig. 1a) is a biologically active
pyrrolylpyrromethene alkaloid whose structure was
first confirmed in 1962 [1]. PG is commonly
produced by Gram-negative bacteria, such as
Serratia spp. and has an eco-physiological role [2].
Its biological activities were extensively researched,
and numerous pharmacological properties were
established, including anticancer and
immunosuppressive However, high cost of extraction and purification
still represent the bottleneck in the microbial
production of PG. Meat and fish processing wastes have high potential as raw materials for conversion
into useful products of higher value. In this study,
meat offcuts were assessed as the sole nutrient for
the fermentative production of PG from S.
marcescens. Using this substrate lowered the
cultivation medium cost and shortened the
fermentation time to 12 h, while allowing a
satisfying PG yield of 83.1 mg/L. The isolated PG
was used in one-step reactions with CuCl₂ or ZnCl₂
in terc-BuOH at 25 °C. The obtained [Cu(PG)Cl] (Fig.
1b) and [Zn(PG)₂] (Fig. 1c) complexes were
characterized by UV-Vis and IR spectroscopy and
their bioactivity potential was assessed.
Antimicrobial activity was assessed in a disc assay
against 4 human pathogens: Escherichia coli NCTC
9001, Pseudomonas aeruginosa ATCC 10332,
Staphylococcus aureus NCTC 6571, Candida
albicans ATCC 10231, but no effect was observed
for the tested concentrations of 200 μg per disc and
lower. However, the anticancer potential of the new
derivatives is promising and the bovine serum
albumin (BSA) binding study revealed that
complexes bind to BSA tightly and reversibly [4].",
journal = "10th Conference of Mikrobiokosmos",
title = "Biotechnological production of bacterial pigment prodigiosin and bioactive properties of its metal complexes with Cu(II) and Zn(II)",
url = "https://hdl.handle.net/21.15107/rcub_imagine_2235"
}
Lazić, J., Milovanović, J., Anejević, T., Ašanin, D., Ilić-Tomić, T., Glišić, B.,& Nikodinović-Runić, J.. (2023). Biotechnological production of bacterial pigment prodigiosin and bioactive properties of its metal complexes with Cu(II) and Zn(II). in 10th Conference of Mikrobiokosmos.
https://hdl.handle.net/21.15107/rcub_imagine_2235
Lazić J, Milovanović J, Anejević T, Ašanin D, Ilić-Tomić T, Glišić B, Nikodinović-Runić J. Biotechnological production of bacterial pigment prodigiosin and bioactive properties of its metal complexes with Cu(II) and Zn(II). in 10th Conference of Mikrobiokosmos. 2023;.
https://hdl.handle.net/21.15107/rcub_imagine_2235 .
Lazić, Jelena, Milovanović, Jelena, Anejević, Tina, Ašanin, Darko, Ilić-Tomić, Tatjana, Glišić, Biljana, Nikodinović-Runić, Jasmina, "Biotechnological production of bacterial pigment prodigiosin and bioactive properties of its metal complexes with Cu(II) and Zn(II)" in 10th Conference of Mikrobiokosmos (2023),
https://hdl.handle.net/21.15107/rcub_imagine_2235 .

Food waste utilization in the production of pyocyanin, a valuable bacterial biopigment

Pantelić, Lena; Lazić, Jelena; Milivojević, Dušan; Nikodinović-Runić, Jasmina

(Beograd : Srpsko hemijsko društvo, 2023)

TY  - CONF
AU  - Pantelić, Lena
AU  - Lazić, Jelena
AU  - Milivojević, Dušan
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1917
AB  - Industrialization, as well as improper waste management, has led to the accumulation
of a large amount of kitchen and food waste, making it omnipresent in every corner of the
world [1]. This waste stream is considered to be a significant portion of the total
biodegradable waste and a major contributor to greenhouse gases induced pollution [2].
According to the Food and Agriculture Organization official data, an astonishing 1.3 billion
tons of food is wasted annually, emphasizing the need to establish multiple biorefining
strategies in order to minimize waste pollution, whilst producing different valuable products
in a sustainable process [3].
PB  - Beograd : Srpsko hemijsko društvo
C3  - 9. simpozijum Hemija i zaštita životne sredine sa međunarodnim učešćem, EnviroChem2023
T1  - Food waste utilization in the production of pyocyanin, a valuable bacterial biopigment
EP  - 172
SP  - 171
VL  - 9
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1917
ER  - 
@conference{
author = "Pantelić, Lena and Lazić, Jelena and Milivojević, Dušan and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "Industrialization, as well as improper waste management, has led to the accumulation
of a large amount of kitchen and food waste, making it omnipresent in every corner of the
world [1]. This waste stream is considered to be a significant portion of the total
biodegradable waste and a major contributor to greenhouse gases induced pollution [2].
According to the Food and Agriculture Organization official data, an astonishing 1.3 billion
tons of food is wasted annually, emphasizing the need to establish multiple biorefining
strategies in order to minimize waste pollution, whilst producing different valuable products
in a sustainable process [3].",
publisher = "Beograd : Srpsko hemijsko društvo",
journal = "9. simpozijum Hemija i zaštita životne sredine sa međunarodnim učešćem, EnviroChem2023",
title = "Food waste utilization in the production of pyocyanin, a valuable bacterial biopigment",
pages = "172-171",
volume = "9",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1917"
}
Pantelić, L., Lazić, J., Milivojević, D.,& Nikodinović-Runić, J.. (2023). Food waste utilization in the production of pyocyanin, a valuable bacterial biopigment. in 9. simpozijum Hemija i zaštita životne sredine sa međunarodnim učešćem, EnviroChem2023
Beograd : Srpsko hemijsko društvo., 9, 171-172.
https://hdl.handle.net/21.15107/rcub_imagine_1917
Pantelić L, Lazić J, Milivojević D, Nikodinović-Runić J. Food waste utilization in the production of pyocyanin, a valuable bacterial biopigment. in 9. simpozijum Hemija i zaštita životne sredine sa međunarodnim učešćem, EnviroChem2023. 2023;9:171-172.
https://hdl.handle.net/21.15107/rcub_imagine_1917 .
Pantelić, Lena, Lazić, Jelena, Milivojević, Dušan, Nikodinović-Runić, Jasmina, "Food waste utilization in the production of pyocyanin, a valuable bacterial biopigment" in 9. simpozijum Hemija i zaštita životne sredine sa međunarodnim učešćem, EnviroChem2023, 9 (2023):171-172,
https://hdl.handle.net/21.15107/rcub_imagine_1917 .

A biotechnological process for the production of pyocyanin and 1-hydroxyphenazine using waste streams from the potato chips industry

Pantelić, Lena; Lazić, Jelena; Nikodinović-Runić, Jasmina; Vojnović, Sandra

(2023)

TY  - CONF
AU  - Pantelić, Lena
AU  - Lazić, Jelena
AU  - Nikodinović-Runić, Jasmina
AU  - Vojnović, Sandra
PY  - 2023
UR  - https://www.accelevents.com/e/circular-bioeconomy-2023
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1923
AB  - Potato industry is one of the major food industries that generates considerable amounts of
potato peels and wastewater (1). These wastes can then be utilized as components of
microbial media in biotechnological production of pyocyanin (PYO) and 1-hydroxyphenazine
(1-HP) using Pseudomonas aeruginosa (2). PYO and 1-HP possess important biological
activities, thus could be applied in the field of medicine, and can be used as biocontrolling
agents (2). However, their application is hindered due to high costs associated with their large
scale production.
In this work, we established a fermentation process which utilizes either potato peels or
potato wastewater as the sole nutrient source to obtain PYO and 1-HP. P. aeruginosa BK25H
strain was selected from our in-house collection. This approach afforded 10 mg/l PYO and
9 mg/l 1-HP using potato wastewater and 15 mg/l PYO and 11 g/l 1-HP using potato peels
after 24 h incubation. This work is the step towards zero-pollution and conversion of waste
to valuable microbial products.
C3  - Biotechnology for a circular bioeconomy: carbon capture, waste recycling and mitigation of global warming
T1  - A biotechnological process for the production of pyocyanin and 1-hydroxyphenazine using waste streams from the potato chips industry
SP  - 53
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1923
ER  - 
@conference{
author = "Pantelić, Lena and Lazić, Jelena and Nikodinović-Runić, Jasmina and Vojnović, Sandra",
year = "2023",
abstract = "Potato industry is one of the major food industries that generates considerable amounts of
potato peels and wastewater (1). These wastes can then be utilized as components of
microbial media in biotechnological production of pyocyanin (PYO) and 1-hydroxyphenazine
(1-HP) using Pseudomonas aeruginosa (2). PYO and 1-HP possess important biological
activities, thus could be applied in the field of medicine, and can be used as biocontrolling
agents (2). However, their application is hindered due to high costs associated with their large
scale production.
In this work, we established a fermentation process which utilizes either potato peels or
potato wastewater as the sole nutrient source to obtain PYO and 1-HP. P. aeruginosa BK25H
strain was selected from our in-house collection. This approach afforded 10 mg/l PYO and
9 mg/l 1-HP using potato wastewater and 15 mg/l PYO and 11 g/l 1-HP using potato peels
after 24 h incubation. This work is the step towards zero-pollution and conversion of waste
to valuable microbial products.",
journal = "Biotechnology for a circular bioeconomy: carbon capture, waste recycling and mitigation of global warming",
title = "A biotechnological process for the production of pyocyanin and 1-hydroxyphenazine using waste streams from the potato chips industry",
pages = "53",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1923"
}
Pantelić, L., Lazić, J., Nikodinović-Runić, J.,& Vojnović, S.. (2023). A biotechnological process for the production of pyocyanin and 1-hydroxyphenazine using waste streams from the potato chips industry. in Biotechnology for a circular bioeconomy: carbon capture, waste recycling and mitigation of global warming, 53.
https://hdl.handle.net/21.15107/rcub_imagine_1923
Pantelić L, Lazić J, Nikodinović-Runić J, Vojnović S. A biotechnological process for the production of pyocyanin and 1-hydroxyphenazine using waste streams from the potato chips industry. in Biotechnology for a circular bioeconomy: carbon capture, waste recycling and mitigation of global warming. 2023;:53.
https://hdl.handle.net/21.15107/rcub_imagine_1923 .
Pantelić, Lena, Lazić, Jelena, Nikodinović-Runić, Jasmina, Vojnović, Sandra, "A biotechnological process for the production of pyocyanin and 1-hydroxyphenazine using waste streams from the potato chips industry" in Biotechnology for a circular bioeconomy: carbon capture, waste recycling and mitigation of global warming (2023):53,
https://hdl.handle.net/21.15107/rcub_imagine_1923 .

Upcycling of food waste streams to valuable biopigments pyocyanin and 1-hydroxyphenazine

Pantelić, Lena; Bogojević Škaro, Sanja; Vojnović, Sandra; Oliveira, Rui; Lazić, Jelena; Ilić-Tomić, Tatjana; Milivojević, Dušan; Nikodinović-Runić, Jasmina

(2023)

TY  - JOUR
AU  - Pantelić, Lena
AU  - Bogojević Škaro, Sanja
AU  - Vojnović, Sandra
AU  - Oliveira, Rui
AU  - Lazić, Jelena
AU  - Ilić-Tomić, Tatjana
AU  - Milivojević, Dušan
AU  - Nikodinović-Runić, Jasmina
PY  - 2023
UR  - https://www.sciencedirect.com/science/article/pii/S0141022923001308
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/2078
AB  - Phenazines, including pyocyanin (PYO) and 1-hydroxyphenazine (1-HP) are extracellular secondary metabolites and multifunctional pigments of Pseudomonas aeruginosa responsible for its blue-green color. These versatile molecules are electrochemically active, involved in significant biological activities giving fitness to the host, but also recognized as antimicrobial and anticancer agents. Their wider application is still limited partly due to the cost of carbon substrate for production, which can be solved by the utilization of carbon from food waste within the biorefinery concept. In this study, a variety of food waste streams (banana peel, potato peel, potato washing, stale bread, yoghurt, processed meat, boiled eggs and mixed canteen waste) was used as sole nutrient source in submerged cultures of P. aeruginosa BK25H. Stale bread was identified as the most suitable substrate to support phenazine biopigments production and bacterial growth. This was further increased in 5-liter fermenter when on average 5.2mgL-1 of PYO and 4.4mgL-1 of 1-HP were purified after 24h batch cultivations from the fermentation medium consisting of homogenized stale bread in tap water. Purified biopigments showed moderate antimicrobial activity, and showed different toxicity profiles, with PYO not being toxic against Caenorhabditis elegans, a free-living soil nematode up to 300µgmL-1 and 1-HP showing lethal effects at 75µgmL-1. Therefore, stale bread waste stream with minimal pretreatment should be considered as suitable biorefinery feedstock, as it can support the production of valuable biopigments such as phenazines.
T2  - Enzyme and Microbial Technology
T1  - Upcycling of food waste streams to valuable biopigments pyocyanin and 1-hydroxyphenazine
SP  - 110322
VL  - 171
DO  - 10.1016/j.enzmictec.2023.110322
ER  - 
@article{
author = "Pantelić, Lena and Bogojević Škaro, Sanja and Vojnović, Sandra and Oliveira, Rui and Lazić, Jelena and Ilić-Tomić, Tatjana and Milivojević, Dušan and Nikodinović-Runić, Jasmina",
year = "2023",
abstract = "Phenazines, including pyocyanin (PYO) and 1-hydroxyphenazine (1-HP) are extracellular secondary metabolites and multifunctional pigments of Pseudomonas aeruginosa responsible for its blue-green color. These versatile molecules are electrochemically active, involved in significant biological activities giving fitness to the host, but also recognized as antimicrobial and anticancer agents. Their wider application is still limited partly due to the cost of carbon substrate for production, which can be solved by the utilization of carbon from food waste within the biorefinery concept. In this study, a variety of food waste streams (banana peel, potato peel, potato washing, stale bread, yoghurt, processed meat, boiled eggs and mixed canteen waste) was used as sole nutrient source in submerged cultures of P. aeruginosa BK25H. Stale bread was identified as the most suitable substrate to support phenazine biopigments production and bacterial growth. This was further increased in 5-liter fermenter when on average 5.2mgL-1 of PYO and 4.4mgL-1 of 1-HP were purified after 24h batch cultivations from the fermentation medium consisting of homogenized stale bread in tap water. Purified biopigments showed moderate antimicrobial activity, and showed different toxicity profiles, with PYO not being toxic against Caenorhabditis elegans, a free-living soil nematode up to 300µgmL-1 and 1-HP showing lethal effects at 75µgmL-1. Therefore, stale bread waste stream with minimal pretreatment should be considered as suitable biorefinery feedstock, as it can support the production of valuable biopigments such as phenazines.",
journal = "Enzyme and Microbial Technology",
title = "Upcycling of food waste streams to valuable biopigments pyocyanin and 1-hydroxyphenazine",
pages = "110322",
volume = "171",
doi = "10.1016/j.enzmictec.2023.110322"
}
Pantelić, L., Bogojević Škaro, S., Vojnović, S., Oliveira, R., Lazić, J., Ilić-Tomić, T., Milivojević, D.,& Nikodinović-Runić, J.. (2023). Upcycling of food waste streams to valuable biopigments pyocyanin and 1-hydroxyphenazine. in Enzyme and Microbial Technology, 171, 110322.
https://doi.org/10.1016/j.enzmictec.2023.110322
Pantelić L, Bogojević Škaro S, Vojnović S, Oliveira R, Lazić J, Ilić-Tomić T, Milivojević D, Nikodinović-Runić J. Upcycling of food waste streams to valuable biopigments pyocyanin and 1-hydroxyphenazine. in Enzyme and Microbial Technology. 2023;171:110322.
doi:10.1016/j.enzmictec.2023.110322 .
Pantelić, Lena, Bogojević Škaro, Sanja, Vojnović, Sandra, Oliveira, Rui, Lazić, Jelena, Ilić-Tomić, Tatjana, Milivojević, Dušan, Nikodinović-Runić, Jasmina, "Upcycling of food waste streams to valuable biopigments pyocyanin and 1-hydroxyphenazine" in Enzyme and Microbial Technology, 171 (2023):110322,
https://doi.org/10.1016/j.enzmictec.2023.110322 . .
3
1

Od otpada do bioterapeutika

Vojnović, Sandra; Stevanović, Milena; Lazić, Jelena; Pantelić, Lena; Milojević, Dušan; Ilić-Tomić, Tatjana; Nikodinović-Runić, Jasmina

(Beograd : Srpsko biološko društvo, 2022)

TY  - CONF
AU  - Vojnović, Sandra
AU  - Stevanović, Milena
AU  - Lazić, Jelena
AU  - Pantelić, Lena
AU  - Milojević, Dušan
AU  - Ilić-Tomić, Tatjana
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1751
AB  - Iako su bioterapeutici doveli do revolucionarnih promena u lečenju raka,
dokazali svoju efikasnost u saniranju mikrobnih infekcija i lečenju ljudi sa
retkim bolestima, zbog visoke cene nisu svima dostupni. Inovativni pristup gde
otpad ulazi u sastav hranjivih podloga za gajenje bakterija bi mogao dovesti do
smanjenja cene bioterapeutika. Fermentacijom na skali od 5 L je dobijeno
nekoliko bioaktivnih prirodnih proizvoda, pri čemu je različit otpad bio izvor
hranjivih materija za gajenje mikroorganizama proizvođača. Prodigiozin,
sekundarni metabolit bakterije Serratia marcescens, dobijen je gajenjem S.
marcescens u tečnoj podlozi sa homogenizovanim mesnim nareskom, a prinos
prodigiozina je poboljšan čak 10 puta u poređenju sa standardnom podlogom.1
Kada je Pseudomonas sp. BK25H gajen u podlozi sa komponentama kuhinjskog otpada
dobijen je odličan prinos piocijanina od 12,5 mg L-1. Slično, aktinomicin D i
staurosporin, sekundarni metaboliti Streptomyces sp. BV365 i 410, su dobijeni
gajenjem proizvođača u hranjivim podlogama sa komponentama poljoprivrednog
otpada ili otpada dobijenog preradom lignoceluloze. S obzirom da neka od
navedenih jedinjenja dostižu komercijalnu vrednost od 2.500,00 evra za 1 mg
(https://www.sigmaaldrich.com/RS/en/product/sigma/s5921), dobijeni rezultati idu u
prilog ideji da bi se otpadne materije mogle koristiti kao jeftine sirovine za
proizvodnju vrednih hemikalija, uz istovremeno smanjenje njihove cene, pri čemu
bi se i količina otpadnih tokova redukovala.
AB  - Иако су биотерапеутици довели до револуционарних промена у лечењу рака,
доказали своју ефикасност у санирању микробних инфекција и лечењу људи са
ретким болестима, због високе цене нису свима доступни. Иновативни приступ где
отпад улази у састав храњивих подлога за гајење бактерија би могао довести до
смањења цене биотерапеутика. Ферментацијом на скали од 5 L је добијено
неколико биоактивних природних производа, при чему је различит отпад био извор
храњивих материја за гајење микроорганизама произвођача. Продигиозин,
секундарни метаболит бактерије Serratia marcescens, добијен је гајењем S.
marcescens у течној подлози са хомогенизованим месним нареском, а принос
продигиозина је побољшан чак 10 пута у поређењу са стандардном подлогом.1
Када је Pseudomonas sp. BK25H гајен у подлози са компонентама кухињског отпада
добијен је одличан принос пиоцијанина од 12,5 mg L-1. Слично, актиномицин Д и
стауроспорин, секундарни метаболити Streptomyces sp. BV365 и 410, су добијени
гајењем произвођача у храњивим подлогама са компонентама пољопривредног
отпада или отпада добијеног прерадом лигноцелулозе. С обзиром да нека од
наведених једињења достижу комерцијалну вредност од 2.500,00 евра за 1 mg
(https://www.sigmaaldrich.com/RS/en/product/sigma/s5921), добијени резултати иду у
прилог идеји да би се отпадне материје могле користити као јефтине сировине за
производњу вредних хемикалија, уз истовремено смањење њихове цене, при чему
би се и количина отпадних токова редуковала.
PB  - Beograd : Srpsko biološko društvo
C3  - Treći kongres biologa Srbije
T1  - Od otpada do bioterapeutika
T1  - Од отпада до биотерапеутика
SP  - 253
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1751
ER  - 
@conference{
author = "Vojnović, Sandra and Stevanović, Milena and Lazić, Jelena and Pantelić, Lena and Milojević, Dušan and Ilić-Tomić, Tatjana and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "Iako su bioterapeutici doveli do revolucionarnih promena u lečenju raka,
dokazali svoju efikasnost u saniranju mikrobnih infekcija i lečenju ljudi sa
retkim bolestima, zbog visoke cene nisu svima dostupni. Inovativni pristup gde
otpad ulazi u sastav hranjivih podloga za gajenje bakterija bi mogao dovesti do
smanjenja cene bioterapeutika. Fermentacijom na skali od 5 L je dobijeno
nekoliko bioaktivnih prirodnih proizvoda, pri čemu je različit otpad bio izvor
hranjivih materija za gajenje mikroorganizama proizvođača. Prodigiozin,
sekundarni metabolit bakterije Serratia marcescens, dobijen je gajenjem S.
marcescens u tečnoj podlozi sa homogenizovanim mesnim nareskom, a prinos
prodigiozina je poboljšan čak 10 puta u poređenju sa standardnom podlogom.1
Kada je Pseudomonas sp. BK25H gajen u podlozi sa komponentama kuhinjskog otpada
dobijen je odličan prinos piocijanina od 12,5 mg L-1. Slično, aktinomicin D i
staurosporin, sekundarni metaboliti Streptomyces sp. BV365 i 410, su dobijeni
gajenjem proizvođača u hranjivim podlogama sa komponentama poljoprivrednog
otpada ili otpada dobijenog preradom lignoceluloze. S obzirom da neka od
navedenih jedinjenja dostižu komercijalnu vrednost od 2.500,00 evra za 1 mg
(https://www.sigmaaldrich.com/RS/en/product/sigma/s5921), dobijeni rezultati idu u
prilog ideji da bi se otpadne materije mogle koristiti kao jeftine sirovine za
proizvodnju vrednih hemikalija, uz istovremeno smanjenje njihove cene, pri čemu
bi se i količina otpadnih tokova redukovala., Иако су биотерапеутици довели до револуционарних промена у лечењу рака,
доказали своју ефикасност у санирању микробних инфекција и лечењу људи са
ретким болестима, због високе цене нису свима доступни. Иновативни приступ где
отпад улази у састав храњивих подлога за гајење бактерија би могао довести до
смањења цене биотерапеутика. Ферментацијом на скали од 5 L је добијено
неколико биоактивних природних производа, при чему је различит отпад био извор
храњивих материја за гајење микроорганизама произвођача. Продигиозин,
секундарни метаболит бактерије Serratia marcescens, добијен је гајењем S.
marcescens у течној подлози са хомогенизованим месним нареском, а принос
продигиозина је побољшан чак 10 пута у поређењу са стандардном подлогом.1
Када је Pseudomonas sp. BK25H гајен у подлози са компонентама кухињског отпада
добијен је одличан принос пиоцијанина од 12,5 mg L-1. Слично, актиномицин Д и
стауроспорин, секундарни метаболити Streptomyces sp. BV365 и 410, су добијени
гајењем произвођача у храњивим подлогама са компонентама пољопривредног
отпада или отпада добијеног прерадом лигноцелулозе. С обзиром да нека од
наведених једињења достижу комерцијалну вредност од 2.500,00 евра за 1 mg
(https://www.sigmaaldrich.com/RS/en/product/sigma/s5921), добијени резултати иду у
прилог идеји да би се отпадне материје могле користити као јефтине сировине за
производњу вредних хемикалија, уз истовремено смањење њихове цене, при чему
би се и количина отпадних токова редуковала.",
publisher = "Beograd : Srpsko biološko društvo",
journal = "Treći kongres biologa Srbije",
title = "Od otpada do bioterapeutika, Од отпада до биотерапеутика",
pages = "253",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1751"
}
Vojnović, S., Stevanović, M., Lazić, J., Pantelić, L., Milojević, D., Ilić-Tomić, T.,& Nikodinović-Runić, J.. (2022). Od otpada do bioterapeutika. in Treći kongres biologa Srbije
Beograd : Srpsko biološko društvo., 253.
https://hdl.handle.net/21.15107/rcub_imagine_1751
Vojnović S, Stevanović M, Lazić J, Pantelić L, Milojević D, Ilić-Tomić T, Nikodinović-Runić J. Od otpada do bioterapeutika. in Treći kongres biologa Srbije. 2022;:253.
https://hdl.handle.net/21.15107/rcub_imagine_1751 .
Vojnović, Sandra, Stevanović, Milena, Lazić, Jelena, Pantelić, Lena, Milojević, Dušan, Ilić-Tomić, Tatjana, Nikodinović-Runić, Jasmina, "Od otpada do bioterapeutika" in Treći kongres biologa Srbije (2022):253,
https://hdl.handle.net/21.15107/rcub_imagine_1751 .

Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives

Lazić, Jelena

(University of Nova Gorica, 2022)

TY  - THES
AU  - Lazić, Jelena
PY  - 2022
UR  - https://repozitorij.ung.si/IzpisGradiva.php?id=7664&lang=eng
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1793
AB  - Prodigiosins (PGs) are a class of bacterial secondary metabolites with remarkable biological activities and colour. In this study, optimised fermentative production of prodigiosin (PG) using waste processed meat as a substrate has been achieved to levels of 83.1 ± 3.0 mg/L from a commercially available Serratia marcescens ATCC 27117 strain within 12 h. Methods were established for the reliable PG extraction from both the bacterial cell pellet and the culture supernatant, while gravitation column chromatography was used to obtain pure bacterial PG. The structure of the isolated PG was optimised by environmentally acceptable oxidative bromination reactions, obtaining mono- and dibrominated derivatives (PG-Br and PG-Br2). Chemical structures were confirmed by structural characterisation using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), showing that PG-Br is a mixture of two monobrominated isomers in approximately equal ratios, while PG-Br2 was afforded as a pure derivative. PG and its brominated derivatives (Br-derivatives) showed anticancer potential with half-maximal inhibitory concentration (IC50) values ranging from 0.62 to 17.00 μg/mL on four tested cancer cell lines (A549 lung, A375 skin, MDA-MB-231 breast, HCT116 colon) and an induction of early apoptosis, but low selectivity against healthy cell lines (MRC-5 lung fibroblasts and HaCaT skin keratinocytes). All three PG, PG-Br and PG-Br2 compounds did not affect roundworms (Caenorhabditis elegans) at concentrations up to 50 μg/mL. However, an improved toxicity profile of Br-derivatives in comparison to the parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 μg/mL applied at 6 h post fertilisation caused death rate of 100, 30 and 0% by PG, PG-Br and PG-Br2, respectively, which is a significant finding for further structural optimisations of bacterial PGs.
AB  - Prodigiozini (PG) so razred obarvanih sekundarnih bakterijskih metabolitov z izjemno biološko aktivnostjo. V doktorski raziskovalni nalogi smo za proizvodnjo prodigiozina uporabili komercialni sev bakterije Serratia marcescens ATCC 27117, kot substrat za fermentacijo pa odpadne produkte procesiranja mesa. Na ta način smo pridobili do 83.1 ± 3.0 prodigiozina v 12-ih urah fermentacije. V nadaljevanju smo vzpostavili metode za ekstrakcijo PS tako iz peleta bakterijskih celic kot tudi iz supernatanta bakterijske kulture. Za pridobitev čistega bakterijskega PG smo uporabili gravitacijsko kolonsko kromatografijo.
Strukturo izoliranega PG smo optimizirali z okolju prijazno metodo oksidativnega bromiranja, pri čemer smo dobili mono- in di-bromirane derivate (PG-Br in PG-Br2). Strukturna karakterizacija bromiranih spojin s pomočjo jedrske magnetne resonance (NMR) in masne spektrometrije (MS) je pokazala, da je PG-Br zmes dveh mono-bromiranih izomer v približno enakih razmerjih, medtem ko je bil PG-Br2 pridobljen kot čisti derivat.
PG in njegove bromirane derivate smo testirali na  štirih rakavih celičnih linijah (A549 – pljučne celice, A375 – kožne celice, MDA-MB-231 – celice raka na prsih in HCT116 – črevesne celice). Potrdili smo antitumorske lastnosti PG in njegovih bromiranih derivatov s polovičnimi maksimalnimi inhibitornimi koncentracijami (IC50) v razponu od 0,62 do 17,00 µg/mL ter indukcijo zgodnje apoptoze, vendar hkrati tudi nizko selektivnost proti zdravim celičnim linijam (MRC-5 - pljučni fibroblasti in HaCaT - kožni keratinociti). Nobena od testiranih PG, PG-Br in PG-Br2 spojin ni imela opaznega vpliva na gliste Caenorhabditis elegans pri koncentracijah do 50 µg/mL. Ugotovili pa smo manjšo toksičnost bromiranih derivatov PG v primerjavi z matičnim PG v modelnem sistemu rib cebric (Danio rerio) in vivo. Pri cebricah, ki so bile 6 ur po oploditvi izpostavljene 10 µg/mL PG, PG-Br oziroma PG-Br2, smo ugotovili 100%, 30% in 0% smrtnost, kar je pomembna ugotovitev za nadaljnjo strukturno optimizacijo bakterijskih PG.
PB  - University of Nova Gorica
T1  - Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives
T1  - Strukturna optimizacija biopigmenta prodigiozin iz bakterije Serratia marcescens ATCC 27117 ter antimikrobne in antitumorske lastnosti novih halogeniranih derivatov
UR  - https://hdl.handle.net/21.15107/rcub_imagine_1793
ER  - 
@phdthesis{
author = "Lazić, Jelena",
year = "2022",
abstract = "Prodigiosins (PGs) are a class of bacterial secondary metabolites with remarkable biological activities and colour. In this study, optimised fermentative production of prodigiosin (PG) using waste processed meat as a substrate has been achieved to levels of 83.1 ± 3.0 mg/L from a commercially available Serratia marcescens ATCC 27117 strain within 12 h. Methods were established for the reliable PG extraction from both the bacterial cell pellet and the culture supernatant, while gravitation column chromatography was used to obtain pure bacterial PG. The structure of the isolated PG was optimised by environmentally acceptable oxidative bromination reactions, obtaining mono- and dibrominated derivatives (PG-Br and PG-Br2). Chemical structures were confirmed by structural characterisation using nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS), showing that PG-Br is a mixture of two monobrominated isomers in approximately equal ratios, while PG-Br2 was afforded as a pure derivative. PG and its brominated derivatives (Br-derivatives) showed anticancer potential with half-maximal inhibitory concentration (IC50) values ranging from 0.62 to 17.00 μg/mL on four tested cancer cell lines (A549 lung, A375 skin, MDA-MB-231 breast, HCT116 colon) and an induction of early apoptosis, but low selectivity against healthy cell lines (MRC-5 lung fibroblasts and HaCaT skin keratinocytes). All three PG, PG-Br and PG-Br2 compounds did not affect roundworms (Caenorhabditis elegans) at concentrations up to 50 μg/mL. However, an improved toxicity profile of Br-derivatives in comparison to the parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 μg/mL applied at 6 h post fertilisation caused death rate of 100, 30 and 0% by PG, PG-Br and PG-Br2, respectively, which is a significant finding for further structural optimisations of bacterial PGs., Prodigiozini (PG) so razred obarvanih sekundarnih bakterijskih metabolitov z izjemno biološko aktivnostjo. V doktorski raziskovalni nalogi smo za proizvodnjo prodigiozina uporabili komercialni sev bakterije Serratia marcescens ATCC 27117, kot substrat za fermentacijo pa odpadne produkte procesiranja mesa. Na ta način smo pridobili do 83.1 ± 3.0 prodigiozina v 12-ih urah fermentacije. V nadaljevanju smo vzpostavili metode za ekstrakcijo PS tako iz peleta bakterijskih celic kot tudi iz supernatanta bakterijske kulture. Za pridobitev čistega bakterijskega PG smo uporabili gravitacijsko kolonsko kromatografijo.
Strukturo izoliranega PG smo optimizirali z okolju prijazno metodo oksidativnega bromiranja, pri čemer smo dobili mono- in di-bromirane derivate (PG-Br in PG-Br2). Strukturna karakterizacija bromiranih spojin s pomočjo jedrske magnetne resonance (NMR) in masne spektrometrije (MS) je pokazala, da je PG-Br zmes dveh mono-bromiranih izomer v približno enakih razmerjih, medtem ko je bil PG-Br2 pridobljen kot čisti derivat.
PG in njegove bromirane derivate smo testirali na  štirih rakavih celičnih linijah (A549 – pljučne celice, A375 – kožne celice, MDA-MB-231 – celice raka na prsih in HCT116 – črevesne celice). Potrdili smo antitumorske lastnosti PG in njegovih bromiranih derivatov s polovičnimi maksimalnimi inhibitornimi koncentracijami (IC50) v razponu od 0,62 do 17,00 µg/mL ter indukcijo zgodnje apoptoze, vendar hkrati tudi nizko selektivnost proti zdravim celičnim linijam (MRC-5 - pljučni fibroblasti in HaCaT - kožni keratinociti). Nobena od testiranih PG, PG-Br in PG-Br2 spojin ni imela opaznega vpliva na gliste Caenorhabditis elegans pri koncentracijah do 50 µg/mL. Ugotovili pa smo manjšo toksičnost bromiranih derivatov PG v primerjavi z matičnim PG v modelnem sistemu rib cebric (Danio rerio) in vivo. Pri cebricah, ki so bile 6 ur po oploditvi izpostavljene 10 µg/mL PG, PG-Br oziroma PG-Br2, smo ugotovili 100%, 30% in 0% smrtnost, kar je pomembna ugotovitev za nadaljnjo strukturno optimizacijo bakterijskih PG.",
publisher = "University of Nova Gorica",
title = "Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives, Strukturna optimizacija biopigmenta prodigiozin iz bakterije Serratia marcescens ATCC 27117 ter antimikrobne in antitumorske lastnosti novih halogeniranih derivatov",
url = "https://hdl.handle.net/21.15107/rcub_imagine_1793"
}
Lazić, J.. (2022). Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives. 
University of Nova Gorica..
https://hdl.handle.net/21.15107/rcub_imagine_1793
Lazić J. Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives. 2022;.
https://hdl.handle.net/21.15107/rcub_imagine_1793 .
Lazić, Jelena, "Structure optimisation of biopigment prodigiosin from Serratia marcescens ATCC 27117 and antimicrobial and anticancer properties of novel halogenated derivatives" (2022),
https://hdl.handle.net/21.15107/rcub_imagine_1793 .

Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117

Lazić, Jelena; Škaro Bogojević, Sanja; Vojnović, Sandra; Aleksić, Ivana; Milivojević, Dušan; Kretzschmar, Martin; Gulder, Tanja; Petković, Milos; Nikodinović-Runić, Jasmina

(MDPI, Basel, 2022)

TY  - JOUR
AU  - Lazić, Jelena
AU  - Škaro Bogojević, Sanja
AU  - Vojnović, Sandra
AU  - Aleksić, Ivana
AU  - Milivojević, Dušan
AU  - Kretzschmar, Martin
AU  - Gulder, Tanja
AU  - Petković, Milos
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1591
AB  - Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62-17.00 mu g/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditis elegans at concentrations up to 50 mu g/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 mu g/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br-2,Br- respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski's "rule of five", with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.
PB  - MDPI, Basel
T2  - Molecules
T1  - Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117
IS  - 12
VL  - 27
DO  - 10.3390/molecules27123729
ER  - 
@article{
author = "Lazić, Jelena and Škaro Bogojević, Sanja and Vojnović, Sandra and Aleksić, Ivana and Milivojević, Dušan and Kretzschmar, Martin and Gulder, Tanja and Petković, Milos and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "Prodigiosins (prodiginines) are a class of bacterial secondary metabolites with remarkable biological activities and color. In this study, optimized production, purification, and characterization of prodigiosin (PG) from easily accessible Serratia marcescens ATCC 27117 strain has been achieved to levels of 14 mg/L of culture within 24 h. Furthermore, environmentally friendly bromination of produced PG was used to afford both novel mono- and dibrominated derivatives of PG. PG and its Br derivatives showed anticancer potential with IC50 values range 0.62-17.00 mu g/mL for all tested cancer cell lines and induction of apoptosis but low selectivity against healthy cell lines. All compounds did not affect Caenorhabditis elegans at concentrations up to 50 mu g/mL. However, an improved toxicity profile of Br derivatives in comparison to parent PG was observed in vivo using zebrafish (Danio rerio) model system, when 10 mu g/mL applied at 6 h post fertilization caused death rate of 100%, 30% and 0% by PG, PG-Br, and PG-Br-2,Br- respectively, which is a significant finding for further structural optimizations of bacterial prodigiosins. The drug-likeness of PG and its Br derivatives was examined, and the novel Br derivatives obey the Lipinski's "rule of five", with an exemption of being more lipophilic than PG, which still makes them good targets for further structural optimization.",
publisher = "MDPI, Basel",
journal = "Molecules",
title = "Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117",
number = "12",
volume = "27",
doi = "10.3390/molecules27123729"
}
Lazić, J., Škaro Bogojević, S., Vojnović, S., Aleksić, I., Milivojević, D., Kretzschmar, M., Gulder, T., Petković, M.,& Nikodinović-Runić, J.. (2022). Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117. in Molecules
MDPI, Basel., 27(12).
https://doi.org/10.3390/molecules27123729
Lazić J, Škaro Bogojević S, Vojnović S, Aleksić I, Milivojević D, Kretzschmar M, Gulder T, Petković M, Nikodinović-Runić J. Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117. in Molecules. 2022;27(12).
doi:10.3390/molecules27123729 .
Lazić, Jelena, Škaro Bogojević, Sanja, Vojnović, Sandra, Aleksić, Ivana, Milivojević, Dušan, Kretzschmar, Martin, Gulder, Tanja, Petković, Milos, Nikodinović-Runić, Jasmina, "Synthesis, Anticancer Potential and Comprehensive Toxicity Studies of Novel Brominated Derivatives of Bacterial Biopigment Prodigiosin from Serratia marcescens ATCC 27117" in Molecules, 27, no. 12 (2022),
https://doi.org/10.3390/molecules27123729 . .
4
15
13

Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation

Stevanović, Nevena; Lazić, Jelena; Kljun, Jakob; Stanković, Mia; Nikodinović-Runić, Jasmina; Turel, Iztok; Djuran, Miloš; Glišić, Biljana

(2022)

TY  - JOUR
AU  - Stevanović, Nevena
AU  - Lazić, Jelena
AU  - Kljun, Jakob
AU  - Stanković, Mia
AU  - Nikodinović-Runić, Jasmina
AU  - Turel, Iztok
AU  - Djuran, Miloš
AU  - Glišić, Biljana
PY  - 2022
UR  - https://www.mdpi.com/2673-9992/14/1/102
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1844
AB  - Recently, we synthesized silver(I) complex with the antifungal agent itraconazole, which showed improved anti-Candida potential and therapeutic safety in comparison to itraconazole and rescued zebrafish embryos affected by lethal C. albicans infection, when used in safe doses. Inspired by these results, in the present study, three new silver(I) complexes with clinically used azoles, econazole (ecz), clotrimazole (ctz) and voriconazole (vcz), [Ag(ecz)2]SbF6 (Ag1), [Ag(ctz)2]SbF6 (Ag2) and {[Ag(vcz)2]SbF6}n (Ag3) were synthesized and structurally characterized by elemental microanalysis, mass spectrometry, spectroscopy (1H NMR, IR and UV-Vis), cyclic voltammetry, molar conductivity measurements, and single crystal X-ray diffraction analysis. The spectroscopic and crystallographic results revealed that, in the synthesized silver(I) complexes, azole ligands are monodentately coordinated to the Ag(I) ion through the nitrogen atom forming [Ag(azole)2]+ complex cation. The antimicrobial effect of complexes and azole ligands was evaluated against different Candida species, as well as Gram-positive and Gram-negative bacteria. The synthesized complexes Ag1-3 exhibited good to moderate antimicrobial activity being, in most cases, more active than the corresponding azole ligands. Complexes Ag2 and Ag3 also showed strong inhibitory activity against C. albicans biofilm formation and strong inhibition of C. albicans filamentation at subinhibitory concentrations.
T2  - Medical Sciences Forum
T2  - Medical Sciences Forum
T1  - Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation
IS  - 1
SP  - 102
VL  - 14
DO  - 10.3390/ECMC2022-13249
ER  - 
@article{
author = "Stevanović, Nevena and Lazić, Jelena and Kljun, Jakob and Stanković, Mia and Nikodinović-Runić, Jasmina and Turel, Iztok and Djuran, Miloš and Glišić, Biljana",
year = "2022",
abstract = "Recently, we synthesized silver(I) complex with the antifungal agent itraconazole, which showed improved anti-Candida potential and therapeutic safety in comparison to itraconazole and rescued zebrafish embryos affected by lethal C. albicans infection, when used in safe doses. Inspired by these results, in the present study, three new silver(I) complexes with clinically used azoles, econazole (ecz), clotrimazole (ctz) and voriconazole (vcz), [Ag(ecz)2]SbF6 (Ag1), [Ag(ctz)2]SbF6 (Ag2) and {[Ag(vcz)2]SbF6}n (Ag3) were synthesized and structurally characterized by elemental microanalysis, mass spectrometry, spectroscopy (1H NMR, IR and UV-Vis), cyclic voltammetry, molar conductivity measurements, and single crystal X-ray diffraction analysis. The spectroscopic and crystallographic results revealed that, in the synthesized silver(I) complexes, azole ligands are monodentately coordinated to the Ag(I) ion through the nitrogen atom forming [Ag(azole)2]+ complex cation. The antimicrobial effect of complexes and azole ligands was evaluated against different Candida species, as well as Gram-positive and Gram-negative bacteria. The synthesized complexes Ag1-3 exhibited good to moderate antimicrobial activity being, in most cases, more active than the corresponding azole ligands. Complexes Ag2 and Ag3 also showed strong inhibitory activity against C. albicans biofilm formation and strong inhibition of C. albicans filamentation at subinhibitory concentrations.",
journal = "Medical Sciences Forum, Medical Sciences Forum",
title = "Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation",
number = "1",
pages = "102",
volume = "14",
doi = "10.3390/ECMC2022-13249"
}
Stevanović, N., Lazić, J., Kljun, J., Stanković, M., Nikodinović-Runić, J., Turel, I., Djuran, M.,& Glišić, B.. (2022). Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation. in Medical Sciences Forum, 14(1), 102.
https://doi.org/10.3390/ECMC2022-13249
Stevanović N, Lazić J, Kljun J, Stanković M, Nikodinović-Runić J, Turel I, Djuran M, Glišić B. Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation. in Medical Sciences Forum. 2022;14(1):102.
doi:10.3390/ECMC2022-13249 .
Stevanović, Nevena, Lazić, Jelena, Kljun, Jakob, Stanković, Mia, Nikodinović-Runić, Jasmina, Turel, Iztok, Djuran, Miloš, Glišić, Biljana, "Silver(I) Complexes with Clinically Used Azoles: Synthesis, Structural Characterization and Antimicrobial Evaluation" in Medical Sciences Forum, 14, no. 1 (2022):102,
https://doi.org/10.3390/ECMC2022-13249 . .

Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies

Keskin, Selbi; Dogan, Sengul Dilem; Gunduz, Miyase Gozde; Aleksić, Ivana; Vojnović, Sandra; Lazić, Jelena; Nikodinović-Runić, Jasmina

(Elsevier, Amsterdam, 2022)

TY  - JOUR
AU  - Keskin, Selbi
AU  - Dogan, Sengul Dilem
AU  - Gunduz, Miyase Gozde
AU  - Aleksić, Ivana
AU  - Vojnović, Sandra
AU  - Lazić, Jelena
AU  - Nikodinović-Runić, Jasmina
PY  - 2022
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1514
AB  - In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies.
PB  - Elsevier, Amsterdam
T2  - Journal of Molecular Structure
T1  - Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies
VL  - 1270
DO  - 10.1016/j.molstruc.2022.133936
ER  - 
@article{
author = "Keskin, Selbi and Dogan, Sengul Dilem and Gunduz, Miyase Gozde and Aleksić, Ivana and Vojnović, Sandra and Lazić, Jelena and Nikodinović-Runić, Jasmina",
year = "2022",
abstract = "In the present study, we report the synthesis, cytotoxicity determination and molecular modeling studies of twelve novel indole-based hydrazone derivatives ( IH1 - IH12 ). To obtain the target molecules, initially, 1 H -indole-2-carboxylic acid and ethanol were heated in the presence of an acid catalyst to yield ethyl 1 H -indole-2-carboxylate. Following the hydrazinolyzation of the ester moiety, the resulting compound, 1 H -indole-2-carbohydrazide reacted with appropriate benzaldehyde derivatives to obtain IH1 - IH12 . The proposed chemical structures of all compounds were confirmed by their 1 H NMR, 13 C NMR, IR, and HRMS data. Additionally, the configuration of C = N bond in IH8 was determined as ( E ) by applying 2D NMR technique, NOESY. Subsequently, the compounds were tested against both colon cancer (HCT116) and lung cancer (A549), as well as healthy lung fibroblast (MRC-5) cell lines to determine their potential as anticancer agents and their selectivity indexes (SI). Based on the obtained data from the antiproliferative MTT assay, HCT116 cell line was more sensitive to our molecules compared to A549. Furthermore, lipophilic halogens were preferable substituents on the phenyl ring for the selective toxicity against cancer cell lines. Drug-likeness analysis carried out by calculating important physicochemical properties of IH1 - IH12 confirmed that they all obey Lipinski's rule of five. Finally, hypoxia inducible factor (HIF)-1 alpha was suggested as the potential biological target of the compounds through molecular docking studies.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Molecular Structure",
title = "Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies",
volume = "1270",
doi = "10.1016/j.molstruc.2022.133936"
}
Keskin, S., Dogan, S. D., Gunduz, M. G., Aleksić, I., Vojnović, S., Lazić, J.,& Nikodinović-Runić, J.. (2022). Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies. in Journal of Molecular Structure
Elsevier, Amsterdam., 1270.
https://doi.org/10.1016/j.molstruc.2022.133936
Keskin S, Dogan SD, Gunduz MG, Aleksić I, Vojnović S, Lazić J, Nikodinović-Runić J. Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies. in Journal of Molecular Structure. 2022;1270.
doi:10.1016/j.molstruc.2022.133936 .
Keskin, Selbi, Dogan, Sengul Dilem, Gunduz, Miyase Gozde, Aleksić, Ivana, Vojnović, Sandra, Lazić, Jelena, Nikodinović-Runić, Jasmina, "Indole-based hydrazone derivatives: Synthesis, cytotoxicity assessment, and molecular modeling studies" in Journal of Molecular Structure, 1270 (2022),
https://doi.org/10.1016/j.molstruc.2022.133936 . .
4
5

Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity

Bozinovi, Nina; Ajdačić, Vladimir; Lazić, Jelena; Lecerf, Maxime; Daventure, Victoria; Nikodinović-Runić, Jasmina; Opsenica, Igor M.; Dimitrov, Jordan D.

(Amer Chemical Soc, Washington, 2019)

TY  - JOUR
AU  - Bozinovi, Nina
AU  - Ajdačić, Vladimir
AU  - Lazić, Jelena
AU  - Lecerf, Maxime
AU  - Daventure, Victoria
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor M.
AU  - Dimitrov, Jordan D.
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1223
AB  - In a healthy immune repertoire, there exists a fraction of polyreactive antibodies that can bind to a variety of unrelated self- and foreign antigens. Apart from naturally polyreactive antibodies, in every healthy individual, there is a fraction of antibody that can gain polyreactivity upon exposure to porphyrin cofactor heme. Molecular mechanisms and biological significance of the appearance of cryptic polyreactivity are not well understood. It is believed that heme acts as an interfacial cofactor between the antibody and the newly recognized antigens. To further test this claim and gain insight into the types of interactions involved in heme binding, we herein investigated the influence of a group of aromatic guanylhydrazone molecules on the heme-induced antibody polyreactivity. From the analysis of SAR and the results of UV-vis absorbance spectroscopy, it was concluded that the most probable mechanism by which the studied molecules inhibit heme-mediated polyreactivity of the antibody is the direct binding to heme, thus preventing heme from binding to antibody and/or antigen. The inhibitory capacity of the most potent compounds was substantially higher than that of chloroquine, a well-known heme binder. Some of the guanylhydrazone molecules were able to induce polyreactivity of the studied antibody themselves, possibly by a mechanism similar to heme. Results described here point to the conclusion that heme indeed must bind to an antibody to induce its polyreactivity, and that both pi-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes.
PB  - Amer Chemical Soc, Washington
T2  - Acs Omega
T1  - Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity
EP  - 20458
IS  - 24
SP  - 20450
VL  - 4
DO  - 10.1021/acsomega.9b01548
ER  - 
@article{
author = "Bozinovi, Nina and Ajdačić, Vladimir and Lazić, Jelena and Lecerf, Maxime and Daventure, Victoria and Nikodinović-Runić, Jasmina and Opsenica, Igor M. and Dimitrov, Jordan D.",
year = "2019",
abstract = "In a healthy immune repertoire, there exists a fraction of polyreactive antibodies that can bind to a variety of unrelated self- and foreign antigens. Apart from naturally polyreactive antibodies, in every healthy individual, there is a fraction of antibody that can gain polyreactivity upon exposure to porphyrin cofactor heme. Molecular mechanisms and biological significance of the appearance of cryptic polyreactivity are not well understood. It is believed that heme acts as an interfacial cofactor between the antibody and the newly recognized antigens. To further test this claim and gain insight into the types of interactions involved in heme binding, we herein investigated the influence of a group of aromatic guanylhydrazone molecules on the heme-induced antibody polyreactivity. From the analysis of SAR and the results of UV-vis absorbance spectroscopy, it was concluded that the most probable mechanism by which the studied molecules inhibit heme-mediated polyreactivity of the antibody is the direct binding to heme, thus preventing heme from binding to antibody and/or antigen. The inhibitory capacity of the most potent compounds was substantially higher than that of chloroquine, a well-known heme binder. Some of the guanylhydrazone molecules were able to induce polyreactivity of the studied antibody themselves, possibly by a mechanism similar to heme. Results described here point to the conclusion that heme indeed must bind to an antibody to induce its polyreactivity, and that both pi-stacking interactions and iron coordination contribute to the binding affinity, while certain structures, such as guanylhydrazones, can interfere with these processes.",
publisher = "Amer Chemical Soc, Washington",
journal = "Acs Omega",
title = "Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity",
pages = "20458-20450",
number = "24",
volume = "4",
doi = "10.1021/acsomega.9b01548"
}
Bozinovi, N., Ajdačić, V., Lazić, J., Lecerf, M., Daventure, V., Nikodinović-Runić, J., Opsenica, I. M.,& Dimitrov, J. D.. (2019). Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. in Acs Omega
Amer Chemical Soc, Washington., 4(24), 20450-20458.
https://doi.org/10.1021/acsomega.9b01548
Bozinovi N, Ajdačić V, Lazić J, Lecerf M, Daventure V, Nikodinović-Runić J, Opsenica IM, Dimitrov JD. Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity. in Acs Omega. 2019;4(24):20450-20458.
doi:10.1021/acsomega.9b01548 .
Bozinovi, Nina, Ajdačić, Vladimir, Lazić, Jelena, Lecerf, Maxime, Daventure, Victoria, Nikodinović-Runić, Jasmina, Opsenica, Igor M., Dimitrov, Jordan D., "Aromatic Guanylhydrazones for the Control of Heme-Induced Antibody Polyreactivity" in Acs Omega, 4, no. 24 (2019):20450-20458,
https://doi.org/10.1021/acsomega.9b01548 . .
1
1
1
1

Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction

Lazić, Jelena; Ajdačić, Vladimir; Vojnović, Sandra; Zlatović, Mario; Pekmezović, Marina; Mogavero, Selene; Opsenica, Igor; Nikodinović-Runić, Jasmina

(Springer, New York, 2018)

TY  - JOUR
AU  - Lazić, Jelena
AU  - Ajdačić, Vladimir
AU  - Vojnović, Sandra
AU  - Zlatović, Mario
AU  - Pekmezović, Marina
AU  - Mogavero, Selene
AU  - Opsenica, Igor
AU  - Nikodinović-Runić, Jasmina
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1195
AB  - Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.
PB  - Springer, New York
T2  - Applied Microbiology and Biotechnology
T1  - Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction
EP  - 1901
IS  - 4
SP  - 1889
VL  - 102
DO  - 10.1007/s00253-018-8749-3
ER  - 
@article{
author = "Lazić, Jelena and Ajdačić, Vladimir and Vojnović, Sandra and Zlatović, Mario and Pekmezović, Marina and Mogavero, Selene and Opsenica, Igor and Nikodinović-Runić, Jasmina",
year = "2018",
abstract = "Candida spp. are leading causes of opportunistic mycoses, including life-threatening hospital-borne infections, and novel antifungals, preferably aiming targets that have not been used before, are constantly needed. Hydrazone-and guanidinecontaining molecules have shown a wide range of biological activities, including recently described excellent antifungal properties. In this study, four bis-guanylhydrazone derivatives (BG1-4) were generated following a previously developed synthetic route. Anti-Candida (two C. albicans, C. glabrata, and C. parapsilosis) minimal inhibitory concentrations (MICs) of bisguanylhydrazones were between 2 and 15.6 mu g/mL. They were also effective against preformed 48-h-old C. albicans biofilms. In vitroDNA interaction, circular dichroism, and molecular docking analysis showed the great ability of these compounds to bind fungal DNA. Competition with DNA-binding stain, exposure of phosphatidylserine at the outer layer of the cytoplasmic membrane, and activation of metacaspases were shown for BG3. This pro-apoptotic effect of BG3 was only partially due to the accumulation of reactive oxygen species in C. albicans, as only twofold MIC and higher concentrations of BG3 caused depolarization of mitochondrial membrane which was accompanied by the decrease of the activity of fungal mitochondrial dehydrogenases, while the activity of oxidative stress response enzymes glutathione reductase and catalase was not significantly affected. BG3 showed synergistic activity with amphotericin B with a fractional inhibitory concentration index of 0.5. It also exerted low cytotoxicity and the ability to inhibit epithelial cell (TR146) invasion and damage by virulent C. albicans SC5314. With further developments, BG3 may further progress in the antifungal pipeline as a DNA-targeting agent.",
publisher = "Springer, New York",
journal = "Applied Microbiology and Biotechnology",
title = "Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction",
pages = "1901-1889",
number = "4",
volume = "102",
doi = "10.1007/s00253-018-8749-3"
}
Lazić, J., Ajdačić, V., Vojnović, S., Zlatović, M., Pekmezović, M., Mogavero, S., Opsenica, I.,& Nikodinović-Runić, J.. (2018). Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. in Applied Microbiology and Biotechnology
Springer, New York., 102(4), 1889-1901.
https://doi.org/10.1007/s00253-018-8749-3
Lazić J, Ajdačić V, Vojnović S, Zlatović M, Pekmezović M, Mogavero S, Opsenica I, Nikodinović-Runić J. Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction. in Applied Microbiology and Biotechnology. 2018;102(4):1889-1901.
doi:10.1007/s00253-018-8749-3 .
Lazić, Jelena, Ajdačić, Vladimir, Vojnović, Sandra, Zlatović, Mario, Pekmezović, Marina, Mogavero, Selene, Opsenica, Igor, Nikodinović-Runić, Jasmina, "Bis-guanylhydrazones as efficient anti-Candida compounds through DNA interaction" in Applied Microbiology and Biotechnology, 102, no. 4 (2018):1889-1901,
https://doi.org/10.1007/s00253-018-8749-3 . .
1
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14

Antibacterial and antifungal properties of guanylhydrazones

Ajdačić, Vladimir; Lazić, Jelena; Mojicević, Marija; Segan, Sandra; Nikodinović-Runić, Jasmina; Opsenica, Igor M.

(Srpsko hemijsko društvo, Beograd, 2017)

TY  - JOUR
AU  - Ajdačić, Vladimir
AU  - Lazić, Jelena
AU  - Mojicević, Marija
AU  - Segan, Sandra
AU  - Nikodinović-Runić, Jasmina
AU  - Opsenica, Igor M.
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1010
AB  - A series of novel guanylhydrazones were designed, synthesized and characterized. All the compounds were screened for their antibacterial and antifungal activity. Compounds 26 and 27 showed excellent antibacterial activities against Staphylococcus aureus ATCC 25923 and Micrococcus luteus ATCC 379 with minimal inhibitory concentrations of 4 ae g mL(-1), and good antifungal activity against Candida parapsilosis ATCC 22019. These results suggested that the selected guanylhydrazones could serve as promising leads for improved antimicrobial development.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Antibacterial and antifungal properties of guanylhydrazones
EP  - 649
IS  - 6
SP  - 641
VL  - 82
DO  - 10.2298/JSC170213033A
ER  - 
@article{
author = "Ajdačić, Vladimir and Lazić, Jelena and Mojicević, Marija and Segan, Sandra and Nikodinović-Runić, Jasmina and Opsenica, Igor M.",
year = "2017",
abstract = "A series of novel guanylhydrazones were designed, synthesized and characterized. All the compounds were screened for their antibacterial and antifungal activity. Compounds 26 and 27 showed excellent antibacterial activities against Staphylococcus aureus ATCC 25923 and Micrococcus luteus ATCC 379 with minimal inhibitory concentrations of 4 ae g mL(-1), and good antifungal activity against Candida parapsilosis ATCC 22019. These results suggested that the selected guanylhydrazones could serve as promising leads for improved antimicrobial development.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Antibacterial and antifungal properties of guanylhydrazones",
pages = "649-641",
number = "6",
volume = "82",
doi = "10.2298/JSC170213033A"
}
Ajdačić, V., Lazić, J., Mojicević, M., Segan, S., Nikodinović-Runić, J.,& Opsenica, I. M.. (2017). Antibacterial and antifungal properties of guanylhydrazones. in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 82(6), 641-649.
https://doi.org/10.2298/JSC170213033A
Ajdačić V, Lazić J, Mojicević M, Segan S, Nikodinović-Runić J, Opsenica IM. Antibacterial and antifungal properties of guanylhydrazones. in Journal of the Serbian Chemical Society. 2017;82(6):641-649.
doi:10.2298/JSC170213033A .
Ajdačić, Vladimir, Lazić, Jelena, Mojicević, Marija, Segan, Sandra, Nikodinović-Runić, Jasmina, Opsenica, Igor M., "Antibacterial and antifungal properties of guanylhydrazones" in Journal of the Serbian Chemical Society, 82, no. 6 (2017):641-649,
https://doi.org/10.2298/JSC170213033A . .
3
3
3

Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening

Rasković, Brankica; Lazić, Jelena; Polović, Natalija

(Wiley, Hoboken, 2016)

TY  - JOUR
AU  - Rasković, Brankica
AU  - Lazić, Jelena
AU  - Polović, Natalija
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/972
AB  - BACKGROUNDThe physiological role of fig latex is to protect the plant from pathogens. Latex is a rich source of proteases, predominantly ficin. Fig latex also contains collagenolytic protease and chitinolytic enzymes. Our aim was to investigate changes in protein composition, enzyme and antifungal activities of fig latex during fruit ripening. RESULTSComparison of latex samples in different time periods showed a uniform increase of protein concentration in chronological order. The content of collagenolytic protease did not differ significantly in the latex samples, while the content of ficin decreased. Ficin-specific activity towards casein was the highest at the beginning of fruit development (about 80 U mg(-1)). Specific milk clotting activity increased as well as the abundance of casein band in the clots. Specific chitinolytic activity at the beginning of flowering was 6.5 times higher than the activity in the period when fruits are ripe. Antifungal activity is the most extensive in spring. CONCLUSIONFicin forms with different casein specificities are present in different proportions during fruit ripening, which is of importance for applications in the dairy industry. The protection mechanism against insects and fungi, which relies on chitinolytic activity, is the most important in the early phases of flowering and is replaced with other strategies over time.
PB  - Wiley, Hoboken
T2  - Journal of the Science of Food and Agriculture
T1  - Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening
EP  - 582
IS  - 2
SP  - 576
VL  - 96
DO  - 10.1002/jsfa.7126
ER  - 
@article{
author = "Rasković, Brankica and Lazić, Jelena and Polović, Natalija",
year = "2016",
abstract = "BACKGROUNDThe physiological role of fig latex is to protect the plant from pathogens. Latex is a rich source of proteases, predominantly ficin. Fig latex also contains collagenolytic protease and chitinolytic enzymes. Our aim was to investigate changes in protein composition, enzyme and antifungal activities of fig latex during fruit ripening. RESULTSComparison of latex samples in different time periods showed a uniform increase of protein concentration in chronological order. The content of collagenolytic protease did not differ significantly in the latex samples, while the content of ficin decreased. Ficin-specific activity towards casein was the highest at the beginning of fruit development (about 80 U mg(-1)). Specific milk clotting activity increased as well as the abundance of casein band in the clots. Specific chitinolytic activity at the beginning of flowering was 6.5 times higher than the activity in the period when fruits are ripe. Antifungal activity is the most extensive in spring. CONCLUSIONFicin forms with different casein specificities are present in different proportions during fruit ripening, which is of importance for applications in the dairy industry. The protection mechanism against insects and fungi, which relies on chitinolytic activity, is the most important in the early phases of flowering and is replaced with other strategies over time.",
publisher = "Wiley, Hoboken",
journal = "Journal of the Science of Food and Agriculture",
title = "Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening",
pages = "582-576",
number = "2",
volume = "96",
doi = "10.1002/jsfa.7126"
}
Rasković, B., Lazić, J.,& Polović, N.. (2016). Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening. in Journal of the Science of Food and Agriculture
Wiley, Hoboken., 96(2), 576-582.
https://doi.org/10.1002/jsfa.7126
Rasković B, Lazić J, Polović N. Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening. in Journal of the Science of Food and Agriculture. 2016;96(2):576-582.
doi:10.1002/jsfa.7126 .
Rasković, Brankica, Lazić, Jelena, Polović, Natalija, "Characterisation of general proteolytic, milk clotting and antifungal activity of Ficus carica latex during fruit ripening" in Journal of the Science of Food and Agriculture, 96, no. 2 (2016):576-582,
https://doi.org/10.1002/jsfa.7126 . .
1
42
19
37

Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT)

Lazić, Jelena; Spasić, Jelena; Francuski, Djordje; Tokić-Vujosević, Zorana; Nikodinović-Runić, Jasmina; Maslak, Veselin; Đokić, Lidija

(Srpsko hemijsko društvo, Beograd, 2016)

TY  - JOUR
AU  - Lazić, Jelena
AU  - Spasić, Jelena
AU  - Francuski, Djordje
AU  - Tokić-Vujosević, Zorana
AU  - Nikodinović-Runić, Jasmina
AU  - Maslak, Veselin
AU  - Đokić, Lidija
PY  - 2016
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/929
AB  - Michael addition of aldehydes to nitro-olefins is an effective method to obtain useful chiral gamma-nitroaldehydes. gamma-Nitroaldehydes are precursors for chiral gamma-aminobutyric acid analogues, which have numerous pharmacological activities and are used for the treatment of neurological disorders. A whole-cell system based on recombinantly expressed 4-oxalocrotonate tautomerase (4-OT) was developed and shown to be an effective biocatalyst for the Michael addition of branched aldehydes to beta-nitrostyrenes. The aim of this study was to investigate the influence of the substitution of the N-terminal proline with lysine and arginine, both containing a reactive epsilon-amino group, on the Michael addition catalyzed by 4-OT. First, the effects of these mutations were examined by in silico analysis, followed by the generation of three terminal lysine mutants. The generated mutants, 4-OT_K, 4-OT_PK and 4-OT_KK were tested for their ability to utilise beta-nitrostyrene (1), (E)-1-nitro-2-(2-thienyl)ethene (2) and trans-p-chloro-beta-nitrostyrene (3) as Michael acceptors with isobutanal (2-methylpropanal) as the donor. For comparison, the lithium salt of lysine was used in the same organocatalytic reactions. In general, the introduction of lysine had a negative effect on Michael additions based on overall product yields. However, additional lysine residues at the N-terminus of the protein resulted in structural changes that enhanced the activity towards 2 and 3. Therefore, the N-terminal proline is important for 4-OT-catalysed Michael-additions, but it is not essential.
PB  - Srpsko hemijsko društvo, Beograd
T2  - Journal of the Serbian Chemical Society
T1  - Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT)
EP  - 881
IS  - 8
SP  - 871
VL  - 81
DO  - 10.2298/JSC160222053L
ER  - 
@article{
author = "Lazić, Jelena and Spasić, Jelena and Francuski, Djordje and Tokić-Vujosević, Zorana and Nikodinović-Runić, Jasmina and Maslak, Veselin and Đokić, Lidija",
year = "2016",
abstract = "Michael addition of aldehydes to nitro-olefins is an effective method to obtain useful chiral gamma-nitroaldehydes. gamma-Nitroaldehydes are precursors for chiral gamma-aminobutyric acid analogues, which have numerous pharmacological activities and are used for the treatment of neurological disorders. A whole-cell system based on recombinantly expressed 4-oxalocrotonate tautomerase (4-OT) was developed and shown to be an effective biocatalyst for the Michael addition of branched aldehydes to beta-nitrostyrenes. The aim of this study was to investigate the influence of the substitution of the N-terminal proline with lysine and arginine, both containing a reactive epsilon-amino group, on the Michael addition catalyzed by 4-OT. First, the effects of these mutations were examined by in silico analysis, followed by the generation of three terminal lysine mutants. The generated mutants, 4-OT_K, 4-OT_PK and 4-OT_KK were tested for their ability to utilise beta-nitrostyrene (1), (E)-1-nitro-2-(2-thienyl)ethene (2) and trans-p-chloro-beta-nitrostyrene (3) as Michael acceptors with isobutanal (2-methylpropanal) as the donor. For comparison, the lithium salt of lysine was used in the same organocatalytic reactions. In general, the introduction of lysine had a negative effect on Michael additions based on overall product yields. However, additional lysine residues at the N-terminus of the protein resulted in structural changes that enhanced the activity towards 2 and 3. Therefore, the N-terminal proline is important for 4-OT-catalysed Michael-additions, but it is not essential.",
publisher = "Srpsko hemijsko društvo, Beograd",
journal = "Journal of the Serbian Chemical Society",
title = "Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT)",
pages = "881-871",
number = "8",
volume = "81",
doi = "10.2298/JSC160222053L"
}
Lazić, J., Spasić, J., Francuski, D., Tokić-Vujosević, Z., Nikodinović-Runić, J., Maslak, V.,& Đokić, L.. (2016). Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT). in Journal of the Serbian Chemical Society
Srpsko hemijsko društvo, Beograd., 81(8), 871-881.
https://doi.org/10.2298/JSC160222053L
Lazić J, Spasić J, Francuski D, Tokić-Vujosević Z, Nikodinović-Runić J, Maslak V, Đokić L. Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT). in Journal of the Serbian Chemical Society. 2016;81(8):871-881.
doi:10.2298/JSC160222053L .
Lazić, Jelena, Spasić, Jelena, Francuski, Djordje, Tokić-Vujosević, Zorana, Nikodinović-Runić, Jasmina, Maslak, Veselin, Đokić, Lidija, "Importance of N-terminal proline for the promiscuous activity of 4-oxalocrotonate tautomerase (4-OT)" in Journal of the Serbian Chemical Society, 81, no. 8 (2016):871-881,
https://doi.org/10.2298/JSC160222053L . .
1
1
1