TY  - JOUR
AU  - Tomović, Katarina
AU  - Ilić, Budimir S.
AU  - Smelcerović, Zaklina
AU  - Miljković, Marija
AU  - Yancheva, Denitsa
AU  - Kojić, Milan
AU  - Mavrova, Anelia Ts
AU  - Kocić, Gordana
AU  - Smelcerović, Andrija
PY  - 2020
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1376
AB  - Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo [3,2-a] benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 mu M, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 mu M. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors
VL  - 315
DO  - 10.1016/j.cbi.2019.108873
ER  - 

@article{
author = "Tomović, Katarina and Ilić, Budimir S. and Smelcerović, Zaklina and Miljković, Marija and Yancheva, Denitsa and Kojić, Milan and Mavrova, Anelia Ts and Kocić, Gordana and Smelcerović, Andrija",
year = "2020",
abstract = "Multiple-targeting compounds might reduce complex polypharmacy of multifactorial diseases, such as diabetes, and contribute to the greater therapeutic success. Targeting reactive oxygen species-producing enzymes, as xanthine oxidase (XO), might suppress progression of diabetes-associated vascular complications. In this study a small series of benzimidazole derivatives (1-9) was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4) and XO. One 1,3-disubstituted-benzimidazole-2-imine (5) and 1,3-thiazolo [3,2-a] benzimidazolone derivative (8) were shown as effective dual DPP-4 and XO inhibitors, with IC50 values lower than 200 mu M, and predicted binding modes with both target enzymes. Both selected dual inhibitors (compounds 5 and 8) did not show cytotoxicity to a greater extent on Caco-2 cells even at concentration of 250 mu M. These structures represent new non-purine scaffolds bearing two therapeutic functionalities, being DPP-4 and XO inhibitors, more favorable in comparison to DPP-4 inhibitors with DPP-4 as a single target due to pleiotropic effects of XO inhibition.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors",
volume = "315",
doi = "10.1016/j.cbi.2019.108873"
}

Tomović, K., Ilić, B. S., Smelcerović, Z., Miljković, M., Yancheva, D., Kojić, M., Mavrova, A. T., Kocić, G.,& Smelcerović, A.. (2020). Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 315.
https://doi.org/10.1016/j.cbi.2019.108873

Tomović K, Ilić BS, Smelcerović Z, Miljković M, Yancheva D, Kojić M, Mavrova AT, Kocić G, Smelcerović A. Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors. in Chemico-Biological Interactions. 2020;315.
doi:10.1016/j.cbi.2019.108873 .

Tomović, Katarina, Ilić, Budimir S., Smelcerović, Zaklina, Miljković, Marija, Yancheva, Denitsa, Kojić, Milan, Mavrova, Anelia Ts, Kocić, Gordana, Smelcerović, Andrija, "Benzimidazole-based dual dipeptidyl peptidase-4 and xanthine oxidase inhibitors" in Chemico-Biological Interactions, 315 (2020),
https://doi.org/10.1016/j.cbi.2019.108873 . .

TY  - JOUR
AU  - Tomović, Katarina
AU  - Ilić, Budimir S.
AU  - Miljković, Marija
AU  - Dimov, Stefan
AU  - Yancheva, Denitsa
AU  - Kojić, Milan
AU  - Mavrova, Anelia T.
AU  - Kocić, Gordana
AU  - Smelcerović, Andrija
PY  - 2019
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1396
AB  - A small library of benzo[4,5]thieno[2,3-d]pyrimidine phthalimide and amine derivatives was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4). The phthalimide derivatives exhibited better activity than the amine precursors, with 2-(2-(3-chlorobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dione (compound 14) as the most effective inhibitor (IC50 = 34.17 +/- 5.11 mu M). The five most potent selected inhibitors did not show cytotoxicity to a greater extent on Caco-2 cells, even at a concentration of 250 mu M. Compound 14 is considered as a novel representative of the rare noncompetitive DPP-4 inhibitors. Molecular docking and dynamics simulation indicated the importance of the Tyr547, Lys554, and Trp629 residues of DPP-4 in the formation of the enzyme-inhibitor complex. These observations could be potentially utilized for the rational design and optimization of novel (structurally similar, with phthalimide moiety, or different) noncompetitive DPP-4 inhibitors, which are anyway rare, but favorable in terms of the saturation of substrate competition.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Archiv Der Pharmazie
T1  - Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4
IS  - 1
VL  - 353
DO  - 10.1002/ardp.201900238
ER  - 

@article{
author = "Tomović, Katarina and Ilić, Budimir S. and Miljković, Marija and Dimov, Stefan and Yancheva, Denitsa and Kojić, Milan and Mavrova, Anelia T. and Kocić, Gordana and Smelcerović, Andrija",
year = "2019",
abstract = "A small library of benzo[4,5]thieno[2,3-d]pyrimidine phthalimide and amine derivatives was evaluated for inhibitory activity against dipeptidyl peptidase-4 (DPP-4). The phthalimide derivatives exhibited better activity than the amine precursors, with 2-(2-(3-chlorobenzyl)-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-yl)isoindoline-1,3-dione (compound 14) as the most effective inhibitor (IC50 = 34.17 +/- 5.11 mu M). The five most potent selected inhibitors did not show cytotoxicity to a greater extent on Caco-2 cells, even at a concentration of 250 mu M. Compound 14 is considered as a novel representative of the rare noncompetitive DPP-4 inhibitors. Molecular docking and dynamics simulation indicated the importance of the Tyr547, Lys554, and Trp629 residues of DPP-4 in the formation of the enzyme-inhibitor complex. These observations could be potentially utilized for the rational design and optimization of novel (structurally similar, with phthalimide moiety, or different) noncompetitive DPP-4 inhibitors, which are anyway rare, but favorable in terms of the saturation of substrate competition.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Archiv Der Pharmazie",
title = "Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4",
number = "1",
volume = "353",
doi = "10.1002/ardp.201900238"
}

Tomović, K., Ilić, B. S., Miljković, M., Dimov, S., Yancheva, D., Kojić, M., Mavrova, A. T., Kocić, G.,& Smelcerović, A.. (2019). Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4. in Archiv Der Pharmazie
Wiley-V C H Verlag Gmbh, Weinheim., 353(1).
https://doi.org/10.1002/ardp.201900238

Tomović K, Ilić BS, Miljković M, Dimov S, Yancheva D, Kojić M, Mavrova AT, Kocić G, Smelcerović A. Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4. in Archiv Der Pharmazie. 2019;353(1).
doi:10.1002/ardp.201900238 .

Tomović, Katarina, Ilić, Budimir S., Miljković, Marija, Dimov, Stefan, Yancheva, Denitsa, Kojić, Milan, Mavrova, Anelia T., Kocić, Gordana, Smelcerović, Andrija, "Benzo[4,5]thieno[2,3-d]pyrimidine phthalimide derivative, one of the rare noncompetitive inhibitors of dipeptidyl peptidase-4" in Archiv Der Pharmazie, 353, no. 1 (2019),
https://doi.org/10.1002/ardp.201900238 . .

TY  - JOUR
AU  - Veselinović, Jovana B.
AU  - Đorđević, Vukica
AU  - Bogdanović, Milena
AU  - Morić, Ivana
AU  - Veselinović, Aleksandar M.
PY  - 2018
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1189
AB  - Antibacterial resistance is a growing public health threat of major concern around the world so development of new therapeutic approaches to prevent bacterial multidrug resistance has become a primary consideration for medicinal chemistry research. QSAR models for the dihydrofolate reductase inhibition with 2,4-diamino-5-(substituted-benzyle)-pyramidine derivatives were developed with further computer-aided design of new derivatives with desired activity. The Monte Carlo method has been used as a computational tool for QSAR modeling. For the representation of molecular structure and optimal descriptor calculation, the simplified molecular input line entry system (SMILES) together with the molecular graph (hydrogen-suppressed graph-HSG, hydrogen-filled graph-HFG, and the graph of atomic orbitals-GAO) was used. One-variable models have been calculated for one data split into training, test, and validation set. The impact of Morgan's extended connectivity index on built QSAR models and outliers was determined. Statistical parameters for the best QSAR model are satisfying. Structural indicators (molecular fragments) responsible for the increase and the decrease of the stated activity are defined, and with the application of defined structural alerts, the computer-aided design of new derivatives with desired activity is presented. Computational experiments presented and applied in this research can satisfactorily predict desired endpoint and can be used further for computer-aided antibacterial drug design.
PB  - Springer/Plenum Publishers, New York
T2  - Structural Chemistry
T1  - QSAR modeling of dihydrofolate reductase inhibitors as a therapeutic target for multiresistant bacteria
EP  - 551
IS  - 2
SP  - 541
VL  - 29
DO  - 10.1007/s11224-017-1051-7
ER  - 

@article{
author = "Veselinović, Jovana B. and Đorđević, Vukica and Bogdanović, Milena and Morić, Ivana and Veselinović, Aleksandar M.",
year = "2018",
abstract = "Antibacterial resistance is a growing public health threat of major concern around the world so development of new therapeutic approaches to prevent bacterial multidrug resistance has become a primary consideration for medicinal chemistry research. QSAR models for the dihydrofolate reductase inhibition with 2,4-diamino-5-(substituted-benzyle)-pyramidine derivatives were developed with further computer-aided design of new derivatives with desired activity. The Monte Carlo method has been used as a computational tool for QSAR modeling. For the representation of molecular structure and optimal descriptor calculation, the simplified molecular input line entry system (SMILES) together with the molecular graph (hydrogen-suppressed graph-HSG, hydrogen-filled graph-HFG, and the graph of atomic orbitals-GAO) was used. One-variable models have been calculated for one data split into training, test, and validation set. The impact of Morgan's extended connectivity index on built QSAR models and outliers was determined. Statistical parameters for the best QSAR model are satisfying. Structural indicators (molecular fragments) responsible for the increase and the decrease of the stated activity are defined, and with the application of defined structural alerts, the computer-aided design of new derivatives with desired activity is presented. Computational experiments presented and applied in this research can satisfactorily predict desired endpoint and can be used further for computer-aided antibacterial drug design.",
publisher = "Springer/Plenum Publishers, New York",
journal = "Structural Chemistry",
title = "QSAR modeling of dihydrofolate reductase inhibitors as a therapeutic target for multiresistant bacteria",
pages = "551-541",
number = "2",
volume = "29",
doi = "10.1007/s11224-017-1051-7"
}

Veselinović, J. B., Đorđević, V., Bogdanović, M., Morić, I.,& Veselinović, A. M.. (2018). QSAR modeling of dihydrofolate reductase inhibitors as a therapeutic target for multiresistant bacteria. in Structural Chemistry
Springer/Plenum Publishers, New York., 29(2), 541-551.
https://doi.org/10.1007/s11224-017-1051-7

Veselinović JB, Đorđević V, Bogdanović M, Morić I, Veselinović AM. QSAR modeling of dihydrofolate reductase inhibitors as a therapeutic target for multiresistant bacteria. in Structural Chemistry. 2018;29(2):541-551.
doi:10.1007/s11224-017-1051-7 .

Veselinović, Jovana B., Đorđević, Vukica, Bogdanović, Milena, Morić, Ivana, Veselinović, Aleksandar M., "QSAR modeling of dihydrofolate reductase inhibitors as a therapeutic target for multiresistant bacteria" in Structural Chemistry, 29, no. 2 (2018):541-551,
https://doi.org/10.1007/s11224-017-1051-7 . .

TY  - JOUR
AU  - Veselinović, Jovana B.
AU  - Veselinović, Aleksandar M.
AU  - Ilić-Tomić, Tatjana
AU  - Davis, Reeta
AU  - O'Connor, Kevin
AU  - Pavić, Aleksandar
AU  - Nikodinović-Runić, Jasmina
PY  - 2017
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/1009
AB  - 7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5 mu g/mL, while did not affect the embryos development and survival at doses  lt = 50 mu g/mL and  lt = 25 mu g/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties. Inhibition of tyrosinase was identified as the possible mode of anti-melanogenic action. Molecular docking studies using the homology model of human tyrosinase as well as adenylate cyclase revealed excellent correlation with experimentally obtained results.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Bioorganic & Medicinal Chemistry
T1  - Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies
EP  - 6296
IS  - 24
SP  - 6286
VL  - 25
DO  - 10.1016/j.bmc.2017.09.021
ER  - 

@article{
author = "Veselinović, Jovana B. and Veselinović, Aleksandar M. and Ilić-Tomić, Tatjana and Davis, Reeta and O'Connor, Kevin and Pavić, Aleksandar and Nikodinović-Runić, Jasmina",
year = "2017",
abstract = "7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5 mu g/mL, while did not affect the embryos development and survival at doses  lt = 50 mu g/mL and  lt = 25 mu g/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties. Inhibition of tyrosinase was identified as the possible mode of anti-melanogenic action. Molecular docking studies using the homology model of human tyrosinase as well as adenylate cyclase revealed excellent correlation with experimentally obtained results.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Bioorganic & Medicinal Chemistry",
title = "Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies",
pages = "6296-6286",
number = "24",
volume = "25",
doi = "10.1016/j.bmc.2017.09.021"
}

Veselinović, J. B., Veselinović, A. M., Ilić-Tomić, T., Davis, R., O'Connor, K., Pavić, A.,& Nikodinović-Runić, J.. (2017). Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies. in Bioorganic & Medicinal Chemistry
Pergamon-Elsevier Science Ltd, Oxford., 25(24), 6286-6296.
https://doi.org/10.1016/j.bmc.2017.09.021

Veselinović JB, Veselinović AM, Ilić-Tomić T, Davis R, O'Connor K, Pavić A, Nikodinović-Runić J. Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies. in Bioorganic & Medicinal Chemistry. 2017;25(24):6286-6296.
doi:10.1016/j.bmc.2017.09.021 .

Veselinović, Jovana B., Veselinović, Aleksandar M., Ilić-Tomić, Tatjana, Davis, Reeta, O'Connor, Kevin, Pavić, Aleksandar, Nikodinović-Runić, Jasmina, "Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies" in Bioorganic & Medicinal Chemistry, 25, no. 24 (2017):6286-6296,
https://doi.org/10.1016/j.bmc.2017.09.021 . .

TY  - JOUR
AU  - Veselinović, Jovana B.
AU  - Kocić, Gordana M.
AU  - Pavić, Aleksandar
AU  - Nikodinović-Runić, Jasmina
AU  - Šenerović, Lidija
AU  - Nikolić, Goran M.
AU  - Veselinović, Aleksandar M.
PY  - 2015
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/856
AB  - A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.
PB  - Elsevier Ireland Ltd, Clare
T2  - Chemico-Biological Interactions
T1  - Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study
EP  - 17
SP  - 10
VL  - 231
DO  - 10.1016/j.cbi.2015.02.011
ER  - 

@article{
author = "Veselinović, Jovana B. and Kocić, Gordana M. and Pavić, Aleksandar and Nikodinović-Runić, Jasmina and Šenerović, Lidija and Nikolić, Goran M. and Veselinović, Aleksandar M.",
year = "2015",
abstract = "A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.",
publisher = "Elsevier Ireland Ltd, Clare",
journal = "Chemico-Biological Interactions",
title = "Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study",
pages = "17-10",
volume = "231",
doi = "10.1016/j.cbi.2015.02.011"
}

Veselinović, J. B., Kocić, G. M., Pavić, A., Nikodinović-Runić, J., Šenerović, L., Nikolić, G. M.,& Veselinović, A. M.. (2015). Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study. in Chemico-Biological Interactions
Elsevier Ireland Ltd, Clare., 231, 10-17.
https://doi.org/10.1016/j.cbi.2015.02.011

Veselinović JB, Kocić GM, Pavić A, Nikodinović-Runić J, Šenerović L, Nikolić GM, Veselinović AM. Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study. in Chemico-Biological Interactions. 2015;231:10-17.
doi:10.1016/j.cbi.2015.02.011 .

Veselinović, Jovana B., Kocić, Gordana M., Pavić, Aleksandar, Nikodinović-Runić, Jasmina, Šenerović, Lidija, Nikolić, Goran M., Veselinović, Aleksandar M., "Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study" in Chemico-Biological Interactions, 231 (2015):10-17,
https://doi.org/10.1016/j.cbi.2015.02.011 . .