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 . .

TY  - JOUR
AU  - Milovanović, Jelena
AU  - Gunduz, Miyase Gozde
AU  - Zerva, Anastasia
AU  - Petković, Milos
AU  - Beskoski, Vladimir
AU  - Thomaidis, Nikolaos S.
AU  - Topakas, Evangelos
AU  - Nikodinović-Runić, Jasmina
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1442
AB  - We describe herein the synthesis and laccase mediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4-DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions.
PB  - MDPI, Basel
T2  - Catalysts
T1  - Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives
IS  - 6
VL  - 11
DO  - 10.3390/catal11060727
ER  - 

@article{
author = "Milovanović, Jelena and Gunduz, Miyase Gozde and Zerva, Anastasia and Petković, Milos and Beskoski, Vladimir and Thomaidis, Nikolaos S. and Topakas, Evangelos and Nikodinović-Runić, Jasmina",
year = "2021",
abstract = "We describe herein the synthesis and laccase mediated oxidation of six novel 1,4-dihydropyridine (DHP)-based hexahydroquinolines (DHP1-DHP3) and decahydroacridines (DHP4-DHP6). We employed different laccase enzymes with varying redox potential to convert DHP1-DHP3 and DHP4-DHP6 to the corresponding pyridine-containing tetrahydroquinoline and octahydroacridine derivatives, respectively. Intensively coloured products were detected in all biocatalytic reactions using laccase from Trametes versicolor (TvLacc), possibly due to the presence of conjugated chromophores formed in products after oxidation. The NMR assessment confirmed that the oxidation product of DHP1 was its corresponding pyridine-bearing tetrahydroquinoline derivative. Laccase from Bacillus subtillis (BacillusLacc) was the most efficient enzyme for this group of substrates using HPLC assessment. Overall, it could be concluded that DHP2 and DHP5, bearing catecholic structures, were easily oxidized by all tested laccases, while DHP3 and DHP6 containing electron-withdrawing nitro-groups are not readily oxidized by laccases. DHP4 with decahydroacridine moiety consisting of three condensed six-membered rings that contribute not only to the volume but also to the higher redox potential of the substrate rendered this compound not to be biotransformed with any of the mentioned enzymes. Overall, we showed that multiple analytical approaches are needed in order to assess biocatalytical reactions.",
publisher = "MDPI, Basel",
journal = "Catalysts",
title = "Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives",
number = "6",
volume = "11",
doi = "10.3390/catal11060727"
}

Milovanović, J., Gunduz, M. G., Zerva, A., Petković, M., Beskoski, V., Thomaidis, N. S., Topakas, E.,& Nikodinović-Runić, J.. (2021). Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives. in Catalysts
MDPI, Basel., 11(6).
https://doi.org/10.3390/catal11060727

Milovanović J, Gunduz MG, Zerva A, Petković M, Beskoski V, Thomaidis NS, Topakas E, Nikodinović-Runić J. Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives. in Catalysts. 2021;11(6).
doi:10.3390/catal11060727 .

Milovanović, Jelena, Gunduz, Miyase Gozde, Zerva, Anastasia, Petković, Milos, Beskoski, Vladimir, Thomaidis, Nikolaos S., Topakas, Evangelos, Nikodinović-Runić, Jasmina, "Synthesis and Laccase-Mediated Oxidation of New Condensed 1,4-Dihydropyridine Derivatives" in Catalysts, 11, no. 6 (2021),
https://doi.org/10.3390/catal11060727 . .

TY  - JOUR
AU  - Simić, Milena
AU  - Petković, Milos
AU  - Jovanović, Predrag
AU  - Jovanović, Milos
AU  - Tasić, Gordana
AU  - Besu, Irina
AU  - Zizak, Zeljko
AU  - Aleksić, Ivana
AU  - Nikodinović-Runić, Jasmina
AU  - Savić, Vladimir
PY  - 2021
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1499
AB  - Several coumarin derivatives with a directly attached azole substituent at C-4 were synthesized and biologically studied for their anticancer properties. The cell lines used for this investigation (HeLa, K-562, MDA-MB-53, and MCF-7) demonstrated different sensitivities. The best response in the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay was shown by K-562 cells, with compounds displaying activity (3c, IC50 3.06 mu M; 4a, IC50 5.24 mu M; 4c, IC50 4.7 mu M) similar to that of cisplatin (IC50 similar to 6 mu M), which was used as the standard. The studied azole-substituted coumarins demonstrated weaker activity toward other cell lines, except for compound 4c, which was equally potent in the case of MCF-7 cells. Additional biological evaluations supported interference with the cell cycle as a potential mechanism of action and confirmed the absence of toxicity in zebrafish embryos. On the basis of these initial results, 4-azole coumarins should be explored further. Although their activity would need additional optimization, the fact that these compounds are fragment-like structures with MW P  lt 3 offers enough flexibility to fine-tune their drug-like properties.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Archiv Der Pharmazie
T1  - Fragment-type 4-azolylcoumarin derivatives with anticancer properties
IS  - 11
VL  - 354
DO  - 10.1002/ardp.202100238
ER  - 

@article{
author = "Simić, Milena and Petković, Milos and Jovanović, Predrag and Jovanović, Milos and Tasić, Gordana and Besu, Irina and Zizak, Zeljko and Aleksić, Ivana and Nikodinović-Runić, Jasmina and Savić, Vladimir",
year = "2021",
abstract = "Several coumarin derivatives with a directly attached azole substituent at C-4 were synthesized and biologically studied for their anticancer properties. The cell lines used for this investigation (HeLa, K-562, MDA-MB-53, and MCF-7) demonstrated different sensitivities. The best response in the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide) assay was shown by K-562 cells, with compounds displaying activity (3c, IC50 3.06 mu M; 4a, IC50 5.24 mu M; 4c, IC50 4.7 mu M) similar to that of cisplatin (IC50 similar to 6 mu M), which was used as the standard. The studied azole-substituted coumarins demonstrated weaker activity toward other cell lines, except for compound 4c, which was equally potent in the case of MCF-7 cells. Additional biological evaluations supported interference with the cell cycle as a potential mechanism of action and confirmed the absence of toxicity in zebrafish embryos. On the basis of these initial results, 4-azole coumarins should be explored further. Although their activity would need additional optimization, the fact that these compounds are fragment-like structures with MW P  lt 3 offers enough flexibility to fine-tune their drug-like properties.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv Der Pharmazie",
title = "Fragment-type 4-azolylcoumarin derivatives with anticancer properties",
number = "11",
volume = "354",
doi = "10.1002/ardp.202100238"
}

Simić, M., Petković, M., Jovanović, P., Jovanović, M., Tasić, G., Besu, I., Zizak, Z., Aleksić, I., Nikodinović-Runić, J.,& Savić, V.. (2021). Fragment-type 4-azolylcoumarin derivatives with anticancer properties. in Archiv Der Pharmazie
Wiley-V C H Verlag Gmbh, Weinheim., 354(11).
https://doi.org/10.1002/ardp.202100238

Simić M, Petković M, Jovanović P, Jovanović M, Tasić G, Besu I, Zizak Z, Aleksić I, Nikodinović-Runić J, Savić V. Fragment-type 4-azolylcoumarin derivatives with anticancer properties. in Archiv Der Pharmazie. 2021;354(11).
doi:10.1002/ardp.202100238 .

Simić, Milena, Petković, Milos, Jovanović, Predrag, Jovanović, Milos, Tasić, Gordana, Besu, Irina, Zizak, Zeljko, Aleksić, Ivana, Nikodinović-Runić, Jasmina, Savić, Vladimir, "Fragment-type 4-azolylcoumarin derivatives with anticancer properties" in Archiv Der Pharmazie, 354, no. 11 (2021),
https://doi.org/10.1002/ardp.202100238 . .