TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Čakar, Mira
AU  - Todorović, Nina
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5589
AB  - The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene
hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in
methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04)
defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa
values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the
distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M
HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and
polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a
concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility
of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10–
3 M HP–β-CD which
was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of
10–
3 M β-CD.
PB  - Springer Nature
T2  - Chemical Papers
T1  - Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride
DO  - 10.1007/s11696-024-03399-1
ER  - 

@article{
author = "Popović-Nikolić, Marija and Čakar, Mira and Todorović, Nina and Nikolić, Katarina and Popović, Gordana",
year = "2024",
abstract = "The acid–base equilibria of raloxifene and the mutual influence of pH and solubility enhancers on the solubility of raloxifene
hydrochloride were studied. The apparent ionization constants (pKa*) of raloxifene were determined potentiometrically in
methanol–water mixtures (45%-55% w/w), and the pKa values (pKa1 = 7.21 ± 0.02, pKa2 = 7.86 ± 0.02, pKa3 = 9.97 ± 0.04)
defining ionization in aqueous media were obtained by extrapolating the pKa* values to 0% of methanol. The obtained pKa
values were assigned to the corresponding ionization centers. Based on the ionization constants obtained in this study, the
distribution of the equilibrium forms of raloxifene was calculated. The solubility of raloxifene hydrochloride in 0.01 M
HCl, acetate buffer pH 4.5 and phosphate buffer pH 6.8 was studied with and without the presence of β-CD, HP-β-CD and
polysorbate 80. The most effective solubility enhancer of raloxifene hydrochloride in 0.01 M HCl was polysorbate 80 at a
concentration of 0.5%, while the influence of this enhancer in phosphate buffer pH 6.8 was negligible. The highest solubility
of raloxifene hydrochloride in acetate and phosphate buffer was achieved in the presence of 10–
3 M HP–β-CD which
was 1.3-fold higher in both 0.01 M HCl and acetate buffer and 2.3-fold higher in phosphate buffer than in the presence of
10–
3 M β-CD.",
publisher = "Springer Nature",
journal = "Chemical Papers",
title = "Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride",
doi = "10.1007/s11696-024-03399-1"
}

Popović-Nikolić, M., Čakar, M., Todorović, N., Nikolić, K.,& Popović, G.. (2024). Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride. in Chemical Papers
Springer Nature..
https://doi.org/10.1007/s11696-024-03399-1

Popović-Nikolić M, Čakar M, Todorović N, Nikolić K, Popović G. Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride. in Chemical Papers. 2024;.
doi:10.1007/s11696-024-03399-1 .

Popović-Nikolić, Marija, Čakar, Mira, Todorović, Nina, Nikolić, Katarina, Popović, Gordana, "Study on protolytic equilibria and the effects of pH, cyclodextrins and polysorbate 80 on solubility of raloxifene hydrochloride" in Chemical Papers (2024),
https://doi.org/10.1007/s11696-024-03399-1 . .

TY  - JOUR
AU  - Beljkaš, Milan
AU  - Ilić, Aleksandra
AU  - Cebzan, Alen
AU  - Radović, Branko
AU  - Đoković, Nemanja
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
AU  - Oljačić, Slavica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5339
AB  - Histone deacetylases (HDACs) are the major regulators of the balance of acetylation of histone and non-histone proteins. In contrast to other HDAC isoforms, HDAC6 is mainly involved in maintaining the acetylation balance of many non-histone proteins. Therefore, the overexpression of HDAC6 is associated with tumorigenesis, invasion, migration, survival, apoptosis and growth of various malignancies. As a result, HDAC6 is considered a promising target for cancer treatment. However, none of selective HDAC6 inhibitors are in clinical use, mainly because of the low efficacy and high concentrations used to show anticancer properties, which may lead to off-target effects. Therefore, HDAC6 inhibitors with dual-target capabilities represent a new trend in cancer treatment, aiming to overcome the above problems. In this review, we summarize the advances in tumor treatment with dual-target HDAC6 inhibitors.
PB  - MDPI
T2  - Pharmaceutics
T1  - Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer
VL  - 15
IS  - 11
DO  - 10.3390/pharmaceutics15112581
ER  - 

@article{
author = "Beljkaš, Milan and Ilić, Aleksandra and Cebzan, Alen and Radović, Branko and Đoković, Nemanja and Ružić, Dušan and Nikolić, Katarina and Oljačić, Slavica",
year = "2023",
abstract = "Histone deacetylases (HDACs) are the major regulators of the balance of acetylation of histone and non-histone proteins. In contrast to other HDAC isoforms, HDAC6 is mainly involved in maintaining the acetylation balance of many non-histone proteins. Therefore, the overexpression of HDAC6 is associated with tumorigenesis, invasion, migration, survival, apoptosis and growth of various malignancies. As a result, HDAC6 is considered a promising target for cancer treatment. However, none of selective HDAC6 inhibitors are in clinical use, mainly because of the low efficacy and high concentrations used to show anticancer properties, which may lead to off-target effects. Therefore, HDAC6 inhibitors with dual-target capabilities represent a new trend in cancer treatment, aiming to overcome the above problems. In this review, we summarize the advances in tumor treatment with dual-target HDAC6 inhibitors.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer",
volume = "15",
number = "11",
doi = "10.3390/pharmaceutics15112581"
}

Beljkaš, M., Ilić, A., Cebzan, A., Radović, B., Đoković, N., Ružić, D., Nikolić, K.,& Oljačić, S.. (2023). Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer. in Pharmaceutics
MDPI., 15(11).
https://doi.org/10.3390/pharmaceutics15112581

Beljkaš M, Ilić A, Cebzan A, Radović B, Đoković N, Ružić D, Nikolić K, Oljačić S. Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer. in Pharmaceutics. 2023;15(11).
doi:10.3390/pharmaceutics15112581 .

Beljkaš, Milan, Ilić, Aleksandra, Cebzan, Alen, Radović, Branko, Đoković, Nemanja, Ružić, Dušan, Nikolić, Katarina, Oljačić, Slavica, "Targeting Histone Deacetylases 6 in Dual-Target Therapy of Cancer" in Pharmaceutics, 15, no. 11 (2023),
https://doi.org/10.3390/pharmaceutics15112581 . .

TY  - JOUR
AU  - Bagán, Andrea
AU  - Rodriguez-Arévalo, Sergio
AU  - Taboada-Jara, Teresa
AU  - Griñán-Ferré, Christian
AU  - Pallàs, Mercè
AU  - Brocos-Mosquera, Iria
AU  - Callado, Luis F.
AU  - Morales-García, José A.
AU  - Pérez, Belén
AU  - Diaz, Caridad
AU  - Fernández-Godino, Rosario
AU  - Genilloud, Olga
AU  - Beljkaš, Milan
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Escolano, Carmen
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5206
AB  - Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer’s disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I2-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I2-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I2-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson’s disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I2-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration.
PB  - MDPI
T2  - Pharmaceutics
T1  - Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease
VL  - 15
IS  - 10
DO  - 10.3390/pharmaceutics15102381
ER  - 

@article{
author = "Bagán, Andrea and Rodriguez-Arévalo, Sergio and Taboada-Jara, Teresa and Griñán-Ferré, Christian and Pallàs, Mercè and Brocos-Mosquera, Iria and Callado, Luis F. and Morales-García, José A. and Pérez, Belén and Diaz, Caridad and Fernández-Godino, Rosario and Genilloud, Olga and Beljkaš, Milan and Oljačić, Slavica and Nikolić, Katarina and Escolano, Carmen",
year = "2023",
abstract = "Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer’s disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I2-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I2-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I2-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson’s disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I2-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease",
volume = "15",
number = "10",
doi = "10.3390/pharmaceutics15102381"
}

Bagán, A., Rodriguez-Arévalo, S., Taboada-Jara, T., Griñán-Ferré, C., Pallàs, M., Brocos-Mosquera, I., Callado, L. F., Morales-García, J. A., Pérez, B., Diaz, C., Fernández-Godino, R., Genilloud, O., Beljkaš, M., Oljačić, S., Nikolić, K.,& Escolano, C.. (2023). Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease. in Pharmaceutics
MDPI., 15(10).
https://doi.org/10.3390/pharmaceutics15102381

Bagán A, Rodriguez-Arévalo S, Taboada-Jara T, Griñán-Ferré C, Pallàs M, Brocos-Mosquera I, Callado LF, Morales-García JA, Pérez B, Diaz C, Fernández-Godino R, Genilloud O, Beljkaš M, Oljačić S, Nikolić K, Escolano C. Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease. in Pharmaceutics. 2023;15(10).
doi:10.3390/pharmaceutics15102381 .

Bagán, Andrea, Rodriguez-Arévalo, Sergio, Taboada-Jara, Teresa, Griñán-Ferré, Christian, Pallàs, Mercè, Brocos-Mosquera, Iria, Callado, Luis F., Morales-García, José A., Pérez, Belén, Diaz, Caridad, Fernández-Godino, Rosario, Genilloud, Olga, Beljkaš, Milan, Oljačić, Slavica, Nikolić, Katarina, Escolano, Carmen, "Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease" in Pharmaceutics, 15, no. 10 (2023),
https://doi.org/10.3390/pharmaceutics15102381 . .

TY  - CONF
AU  - Ružić, Dušan
AU  - Petković, Miloš
AU  - Đoković, Nemanja
AU  - Santibanez, Juan
AU  - Pavić, Aleksandar
AU  - Ganesan, A.
AU  - Srdić Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5074
AB  - Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the absence of specific molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In the era of precision oncology, it is recognized that an imbalance in post-translational modifications of histones, such as histone lysine acetylation and deacetylation, is closely linked to tumor initiation and progression. Two groups of enzymes control the reversible nature of histone post-translational acetylation: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Isoform-specific targeting of HDACs is considered a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, non-selective HDAC inhibitors have been more extensively studied in clinical trials. This work presents the design and discovery of potent HDAC inhibitors that selectively target HDAC6 isozyme, using 1-benzhydryl piperazine as a surface recognition group with different hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with nanomolar IC50 values and two non-selective HDAC inhibitors were identified. Structure-based molecular modelling was utilized to investigate the impact of linker chemistry on the potency of synthesized inhibitors against HDAC6. The anti-cancer, anti-migratory, and anti-invasive activities of these compounds were evaluated using breast cancer cell lines (MDA-MB-231 and MCF-7). Experiments on a zebrafish MDA-MB-231 xenograft model demonstrated that a novel non-selective HDAC inhibitor (8b) with a seven-carbon-atom linker exhibited potent effects against tumor growth, metastasis, and angiogenesis at low micromolar concentrations.
PB  - Serbian Association on for Cancer Research Belgrade, Serbia
C3  - Oncology
Insights
T1  - Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study
VL  - 1
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5074
ER  - 

@conference{
author = "Ružić, Dušan and Petković, Miloš and Đoković, Nemanja and Santibanez, Juan and Pavić, Aleksandar and Ganesan, A. and Srdić Rajić, Tatjana and Nikolić, Katarina",
year = "2023",
abstract = "Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer that has poor survival rates due to the absence of specific molecular markers such as estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). In the era of precision oncology, it is recognized that an imbalance in post-translational modifications of histones, such as histone lysine acetylation and deacetylation, is closely linked to tumor initiation and progression. Two groups of enzymes control the reversible nature of histone post-translational acetylation: histone acetyltransferases (HATs) and histone deacetylases (HDACs). Isoform-specific targeting of HDACs is considered a rational strategy to develop safe anticancer therapeutics compared to non-selective HDAC inhibitors. However, non-selective HDAC inhibitors have been more extensively studied in clinical trials. This work presents the design and discovery of potent HDAC inhibitors that selectively target HDAC6 isozyme, using 1-benzhydryl piperazine as a surface recognition group with different hydrocarbon linkers. Through in vitro screening, two HDAC6-selective inhibitors with nanomolar IC50 values and two non-selective HDAC inhibitors were identified. Structure-based molecular modelling was utilized to investigate the impact of linker chemistry on the potency of synthesized inhibitors against HDAC6. The anti-cancer, anti-migratory, and anti-invasive activities of these compounds were evaluated using breast cancer cell lines (MDA-MB-231 and MCF-7). Experiments on a zebrafish MDA-MB-231 xenograft model demonstrated that a novel non-selective HDAC inhibitor (8b) with a seven-carbon-atom linker exhibited potent effects against tumor growth, metastasis, and angiogenesis at low micromolar concentrations.",
publisher = "Serbian Association on for Cancer Research Belgrade, Serbia",
journal = "Oncology
Insights",
title = "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study",
volume = "1",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5074"
}

Ružić, D., Petković, M., Đoković, N., Santibanez, J., Pavić, A., Ganesan, A., Srdić Rajić, T.,& Nikolić, K.. (2023). Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study. in Oncology
Insights
Serbian Association on for Cancer Research Belgrade, Serbia., 1.
https://hdl.handle.net/21.15107/rcub_farfar_5074

Ružić D, Petković M, Đoković N, Santibanez J, Pavić A, Ganesan A, Srdić Rajić T, Nikolić K. Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study. in Oncology
Insights. 2023;1.
https://hdl.handle.net/21.15107/rcub_farfar_5074 .

Ružić, Dušan, Petković, Miloš, Đoković, Nemanja, Santibanez, Juan, Pavić, Aleksandar, Ganesan, A., Srdić Rajić, Tatjana, Nikolić, Katarina, "Discovery of novel HDAC inhibitors for therapy of triple-negative breast cancer – preclinical study" in Oncology
Insights, 1 (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5074 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Popović, Gordana
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5045
AB  - The protolytic equilibria of bilastine were studied experimentally and theoretically. The
pKa values were determined potentiometrically at a constant ionic strength (0.1 M NaCl) and
temperature 25 °C. Energy calculation of the optimized structures of the equilibrium forms was
performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of
the theoretical study helped to define the ionization profile of bilastine and to assign the
experimentally determined pKa values to the corresponding ionizable groups.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
T1  - Theoretical and experimental study of bilastine ionization
SP  - 427
EP  - 430
DO  - 10.46793/ICCBI23.427PN
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Popović, Gordana and Oljačić, Slavica and Nikolić, Katarina",
year = "2023",
abstract = "The protolytic equilibria of bilastine were studied experimentally and theoretically. The
pKa values were determined potentiometrically at a constant ionic strength (0.1 M NaCl) and
temperature 25 °C. Energy calculation of the optimized structures of the equilibrium forms was
performed at the B3LYP/6-31G (d,p) level of the Density Functional Theory (DFT). The results of
the theoretical study helped to define the ionization profile of bilastine and to assign the
experimentally determined pKa values to the corresponding ionizable groups.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS",
title = "Theoretical and experimental study of bilastine ionization",
pages = "427-430",
doi = "10.46793/ICCBI23.427PN"
}

Popović-Nikolić, M., Popović, G., Oljačić, S.,& Nikolić, K.. (2023). Theoretical and experimental study of bilastine ionization. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 427-430.
https://doi.org/10.46793/ICCBI23.427PN

Popović-Nikolić M, Popović G, Oljačić S, Nikolić K. Theoretical and experimental study of bilastine ionization. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:427-430.
doi:10.46793/ICCBI23.427PN .

Popović-Nikolić, Marija, Popović, Gordana, Oljačić, Slavica, Nikolić, Katarina, "Theoretical and experimental study of bilastine ionization" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):427-430,
https://doi.org/10.46793/ICCBI23.427PN . .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Aleksić, Mara
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5044
AB  - he redox properties of two quinoxaline derivatives, brimonidine and varenicline,
previously studied electrochemically, were evaluated by performing a computational study. On
the basis of some useful quantum chemical parameters the differences and similarities between
their redox features were explained. The obtained results support the experimental findings that
the redox processes of both compounds are under strong influence of the solution pH, whereas
the reduction of brimonidine occurs easier than the reduction of varenicline, at corresponding pH
values.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
T1  - DFT approach of the redox properties of brimonidine and varenicline
SP  - 423
EP  - 426
DO  - 10.46793/ICCBI23.423PN
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Nikolić, Katarina and Aleksić, Mara",
year = "2023",
abstract = "he redox properties of two quinoxaline derivatives, brimonidine and varenicline,
previously studied electrochemically, were evaluated by performing a computational study. On
the basis of some useful quantum chemical parameters the differences and similarities between
their redox features were explained. The obtained results support the experimental findings that
the redox processes of both compounds are under strong influence of the solution pH, whereas
the reduction of brimonidine occurs easier than the reduction of varenicline, at corresponding pH
values.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS",
title = "DFT approach of the redox properties of brimonidine and varenicline",
pages = "423-426",
doi = "10.46793/ICCBI23.423PN"
}

Popović-Nikolić, M., Nikolić, K.,& Aleksić, M.. (2023). DFT approach of the redox properties of brimonidine and varenicline. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 423-426.
https://doi.org/10.46793/ICCBI23.423PN

Popović-Nikolić M, Nikolić K, Aleksić M. DFT approach of the redox properties of brimonidine and varenicline. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:423-426.
doi:10.46793/ICCBI23.423PN .

Popović-Nikolić, Marija, Nikolić, Katarina, Aleksić, Mara, "DFT approach of the redox properties of brimonidine and varenicline" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):423-426,
https://doi.org/10.46793/ICCBI23.423PN . .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Popović, Gordana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5013
PB  - European Research Network on Signal Transduction CA18133
C3  - 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event
T1  - The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems
SP  - 35
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5013
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Oljačić, Slavica and Popović, Gordana and Nikolić, Katarina",
year = "2023",
publisher = "European Research Network on Signal Transduction CA18133",
journal = "3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event",
title = "The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems",
pages = "35",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5013"
}

Popović-Nikolić, M., Oljačić, S., Popović, G.,& Nikolić, K.. (2023). The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems. in 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event
European Research Network on Signal Transduction CA18133., 35.
https://hdl.handle.net/21.15107/rcub_farfar_5013

Popović-Nikolić M, Oljačić S, Popović G, Nikolić K. The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems. in 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event. 2023;:35.
https://hdl.handle.net/21.15107/rcub_farfar_5013 .

Popović-Nikolić, Marija, Oljačić, Slavica, Popović, Gordana, Nikolić, Katarina, "The ionization of a cysteinyl leukotriene receptor antagonist, montelukast, in the presence of biomembrane mimetic systems" in 3rd Transatlantic ECI GPCR Symposium - Early Career Investigators – September 7-8, 2023, Online event (2023):35,
https://hdl.handle.net/21.15107/rcub_farfar_5013 .

TY  - CONF
AU  - Popović-Nikolić, Marija
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5004
AB  - Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults
as well as in pediatric patients 6 months of age and older. Because it is associated with
numerous side effects, including neuropsychiatric events, it is very important to monitor its
pharmacologic behavior when administered chronically. To gain better insight into the
pharmacological properties of ionizable drugs, their physicochemical properties should be
studied under conditions more similar to physiological, such as micellar solutions of
surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic
(carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar
solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX-
100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M NaCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems
SP  - 49
EP  - 49
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5004
ER  - 

@conference{
author = "Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina and Popović, Gordana",
year = "2023",
abstract = "Montelukast is a leukotriene receptor antagonist indicated for asthma prophylaxis in adults
as well as in pediatric patients 6 months of age and older. Because it is associated with
numerous side effects, including neuropsychiatric events, it is very important to monitor its
pharmacologic behavior when administered chronically. To gain better insight into the
pharmacological properties of ionizable drugs, their physicochemical properties should be
studied under conditions more similar to physiological, such as micellar solutions of
surfactants as biomembrane mimetic systems. Montelukast is an ampholyte with one acidic
(carboxyl) and one basic (quinoline nitrogen) group. In this study the effects of micellar
solutions of differently charged surfactants (anionic SDS, cationic CTAB, and nonionic TX-
100) on protolytic equilibria of montelukast were investigated potentiometrically. Solutions were titrated with standard NaOH solution (0.1017 M) at a constant ionic strength (0.1 M NaCl) and a temperature 25°C. Experimental data were analyzed using the Hyperquad program. Due to poor water solubility, the pKa values defining the ionization in water (pKa1 =4.07, pKa2 = 5.49), were obtained indirectly by extrapolation from the pKa* values determined potentiometrically in the different methanol-water mixtures (40%, 50%, and 55% wt/wt). The pKa values in 0.01M micellar solutions were determined without the use of cosolvent. Micelles contributed to the shift in protolytic equilibria of montelukast, anionic ΔpKa up to +1.20, cationic ΔpKa up to +0.27, and nonionic ΔpKa up to +0.98. More pronounced effects are observed on the ionization of carboxyl group than quinoline nitrogen. A change in the distribution of equilibrium forms in a relation to pure water, can be expected in physiological conditions, in interactions of montelukast with polar or charged biomolecules.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems",
pages = "49-49",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5004"
}

Popović-Nikolić, M., Oljačić, S., Nikolić, K.,& Popović, G.. (2023). Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 49-49.
https://hdl.handle.net/21.15107/rcub_farfar_5004

Popović-Nikolić M, Oljačić S, Nikolić K, Popović G. Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:49-49.
https://hdl.handle.net/21.15107/rcub_farfar_5004 .

Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, Popović, Gordana, "Study of ionization of montelukast in differently charged micellar solutions as biomembrane mimetic systems" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):49-49,
https://hdl.handle.net/21.15107/rcub_farfar_5004 .

TY  - JOUR
AU  - Popović-Nikolić, Marija
AU  - Nikolić, Katarina
AU  - Popović, Gordana
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4687
AB  - The acid–base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and rami-
pril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The pKa values were potentiometrically
determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the
computer program Hyperquad. On the basis of the shift in the pKa values (ΔpKa ) determined in micellar media in relation
to the pKa values previously determined in “pure” water, the effect of Brij 35 micelles on ACEIs ionization was estimated.
The presence of nonionic Brij 35 micelles caused a shift in the pKa values of all ionizable groups of the investigated ACEIs
(ΔpKa from − 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular
form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs
and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that
ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which
potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium
forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4–8, which includes
biopharmaceutically important pH values.
PB  - Springer
T2  - Monatshefte für Chemie - Chemical Monthly
T1  - Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35
VL  - 154
SP  - 615
EP  - 624
DO  - 10.1007/s00706-023-03059-2
ER  - 

@article{
author = "Popović-Nikolić, Marija and Nikolić, Katarina and Popović, Gordana",
year = "2023",
abstract = "The acid–base equilibria of six ACE inhibitors (ACEIs), captopril, cilazapril, enalapril, lisinopril, quinapril, and rami-
pril, were investigated in the presence of micelles of nonionic surfactant Brij 35. The pKa values were potentiometrically
determined at 25 °C and at a constant ionic strength (0.1 M NaCl). The obtained potentiometric data were evaluated in the
computer program Hyperquad. On the basis of the shift in the pKa values (ΔpKa ) determined in micellar media in relation
to the pKa values previously determined in “pure” water, the effect of Brij 35 micelles on ACEIs ionization was estimated.
The presence of nonionic Brij 35 micelles caused a shift in the pKa values of all ionizable groups of the investigated ACEIs
(ΔpKa from − 3.44 to + 1.9) while shifting the protolytic equilibria of both acidic and basic groups toward the molecular
form. The Brij 35 micelles expressed the most pronounced effect on the ionization of captopril among the investigated ACEIs
and stronger effect on the ionization of amino than on the ionization of carboxyl groups. The obtained results suggest that
ionizable functional groups of ACEIs are involved in interactions with palisade layer of nonionic Brij 35 micelles, which
potentially can be considered in physiological conditions. Distribution diagrams of the investigated ACEIs equilibrium
forms as a function of pH indicate that the change in distribution is most strongly expressed in pH range 4–8, which includes
biopharmaceutically important pH values.",
publisher = "Springer",
journal = "Monatshefte für Chemie - Chemical Monthly",
title = "Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35",
volume = "154",
pages = "615-624",
doi = "10.1007/s00706-023-03059-2"
}

Popović-Nikolić, M., Nikolić, K.,& Popović, G.. (2023). Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35. in Monatshefte für Chemie - Chemical Monthly
Springer., 154, 615-624.
https://doi.org/10.1007/s00706-023-03059-2

Popović-Nikolić M, Nikolić K, Popović G. Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35. in Monatshefte für Chemie - Chemical Monthly. 2023;154:615-624.
doi:10.1007/s00706-023-03059-2 .

Popović-Nikolić, Marija, Nikolić, Katarina, Popović, Gordana, "Protolytic equilibria of ACE inhibitors in micellar solution of nonionic surfactant Brij 35" in Monatshefte für Chemie - Chemical Monthly, 154 (2023):615-624,
https://doi.org/10.1007/s00706-023-03059-2 . .

TY  - CONF
AU  - Beljkaš, Milan
AU  - Rebić, Jelena
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5043
AB  - Rho-associated coiled-coil kinases (ROCKs) are involved in essential
cellular functions such as adhesion, contraction, motility, proliferation, and cell
survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and
are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and
graft-versus-host disease (belumosudil). Recent studies have focused on exploring the
role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK
inhibitors. The main objective of this study was to identify critical structural features
relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative
structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created
and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚���������
2̅̅̅
and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were
identified (e.g., heterocycle with hydrogen donor group like nitrogen atom) and further
structural modifications of the ROCK1 inhibitors that contribute to increased activity
were proposed (removal of the amino group of the oxadiazole, modification of the
substituents of the phenyl ring).
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS
T1  - 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors
SP  - 1584
EP  - 1588
DO  - 10.46793/ICCBI23.584B
ER  - 

@conference{
author = "Beljkaš, Milan and Rebić, Jelena and Radan, Milica and Đikić, Teodora and Oljačić, Slavica and Nikolić, Katarina",
year = "2023",
abstract = "Rho-associated coiled-coil kinases (ROCKs) are involved in essential
cellular functions such as adhesion, contraction, motility, proliferation, and cell
survival/apoptosis. Four ROCK inhibitors have already been approved by the FDA and
are used to treat glaucoma (ripasudil and netarsudil), cerebral vasospasm (fasudil), and
graft-versus-host disease (belumosudil). Recent studies have focused on exploring the
role of ROCK kinase inhibitors in cancer treatment and the development of new ROCK
inhibitors. The main objective of this study was to identify critical structural features
relevant to the inhibition of ROCK1 using a ligand-based 3D-QSAR (3D quantitative
structure-activity relationship) method. The 3D-QSAR model for ROCK1 was created
and validated using internal and external validation parameters (R2, Q2, R2pred, rm2, r/2m, 𝑟���������𝑚���������
2̅̅̅
and ∆r2m). The main structural features that correlate with the inhibition of ROCK1 were
identified (e.g., heterocycle with hydrogen donor group like nitrogen atom) and further
structural modifications of the ROCK1 inhibitors that contribute to increased activity
were proposed (removal of the amino group of the oxadiazole, modification of the
substituents of the phenyl ring).",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS",
title = "3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors",
pages = "1584-1588",
doi = "10.46793/ICCBI23.584B"
}

Beljkaš, M., Rebić, J., Radan, M., Đikić, T., Oljačić, S.,& Nikolić, K.. (2023). 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 1584-1588.
https://doi.org/10.46793/ICCBI23.584B

Beljkaš M, Rebić J, Radan M, Đikić T, Oljačić S, Nikolić K. 3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS. 2023;:1584-1588.
doi:10.46793/ICCBI23.584B .

Beljkaš, Milan, Rebić, Jelena, Radan, Milica, Đikić, Teodora, Oljačić, Slavica, Nikolić, Katarina, "3D-Quantitative Structure-Activity Relationship and design of novel Rho- associated protein kinases-1 (ROCK1) inhibitors" in 2nd International Conference on Chemo and Bioinformatics, BOOK OF PROOCEEDINGS (2023):1584-1588,
https://doi.org/10.46793/ICCBI23.584B . .

TY  - CONF
AU  - Beljkaš, Milan
AU  - Rebić, Jelena
AU  - Radan, Milica
AU  - Đikić, Teodora
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5041
AB  - Overexpression of Rho-associated protein kinases has been associated with various
diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment.
However, some of them have been shown to have anti-tumor potential. The main objective of this
study was to develop novel ROCK1 inhibitors using the structure-based method, molecular
docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key
interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds
between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating
possible structural changes in the hinge region of studied compounds. On the other hand, the
lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising
approach for further structural modifications in order to design more effective ROCK1 inhibitors.
All the important interactions between the developed ROCK1 inhibitors and the binding site
of the enzyme were established. They also showed acceptable pharmacokinetic properties and
could be further used for synthesis and evaluation by various biological assays.
PB  - Institute for Information Technologies, University of Kragujevac, Serbia
C3  - 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
T1  - Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors
SP  - 1589
EP  - 1592
DO  - 10.46793/ICCBI23.589B
ER  - 

@conference{
author = "Beljkaš, Milan and Rebić, Jelena and Radan, Milica and Đikić, Teodora and Oljačić, Slavica and Nikolić, Katarina",
year = "2023",
abstract = "Overexpression of Rho-associated protein kinases has been associated with various
diseases, including tumors. None of the approved ROCK inhibitors are used for cancer treatment.
However, some of them have been shown to have anti-tumor potential. The main objective of this
study was to develop novel ROCK1 inhibitors using the structure-based method, molecular
docking, and prediction of pharmacokinetic properties using the ADMET predictor. The key
interactions that strongly correlate with the activity of ROCK1 inhibitors are hydrogen bonds
between amino acid residues Met156, Glu154 and the hinge region of the inhibitors, indicating
possible structural changes in the hinge region of studied compounds. On the other hand, the
lack of interactions between 1,3-benzoxadiol moiety and the enzyme presents a promising
approach for further structural modifications in order to design more effective ROCK1 inhibitors.
All the important interactions between the developed ROCK1 inhibitors and the binding site
of the enzyme were established. They also showed acceptable pharmacokinetic properties and
could be further used for synthesis and evaluation by various biological assays.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS",
title = "Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors",
pages = "1589-1592",
doi = "10.46793/ICCBI23.589B"
}

Beljkaš, M., Rebić, J., Radan, M., Đikić, T., Oljačić, S.,& Nikolić, K.. (2023). Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS
Institute for Information Technologies, University of Kragujevac, Serbia., 1589-1592.
https://doi.org/10.46793/ICCBI23.589B

Beljkaš M, Rebić J, Radan M, Đikić T, Oljačić S, Nikolić K. Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors. in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS. 2023;:1589-1592.
doi:10.46793/ICCBI23.589B .

Beljkaš, Milan, Rebić, Jelena, Radan, Milica, Đikić, Teodora, Oljačić, Slavica, Nikolić, Katarina, "Virtual Docking, design and in silico ADMET profiling of novel Rho- associated protein kinases-1 (ROCK1) inhibitors" in 2nd International Conference on Chemo and Bioinformatics ICCBIKG 2023, BOOK OF PROCEEDINGS (2023):1589-1592,
https://doi.org/10.46793/ICCBI23.589B . .

TY  - CONF
AU  - Beljkaš, Milan
AU  - Petković, Miloš
AU  - Nikolić, Katarina
AU  - Oljačić, Slavica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5005
AB  - Histone deacetylases (HDACs) belong to a family of epigenetic enzymes that has 18 different
isoforms and play an important role in the development and progression of various tumors.
To date, five histone deacetylase inhibitors have been approved by the FDA, and are used
to treat multiple myeloma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and
breast cancer (estrogen and/or progesterone positive) [1]. All of them are non-selective.
Therefore, their safety profile is poor and their efficacy is low in single therapy. One of our
previous research projects demonstrated the synergistic effect of HDAC inhibitors and
inhibitors of Rho-associated protein kinases (ROCK) in the treatment of pancreatic ductal
adenocarcinoma (PDAC) [2]. This finding led us to design of the dual HDAC/ROCK inhibitors
with potential effects on PDAC by using structure-based molecular docking method.
Molecular docking study was performed using GOLD software. The crystal structures of
ROCK1 (PDB: 6E9W), ROCK2 (PDB: 7JNT), HDAC1 (PDB: 5ICN), and HDAC6 (PDB: 5EDU)
enzymes were downloaded from the Protein Data Bank (PDB). The enzymes were prepared
for docking study using the online software Play Molecule-ProteinPrepare. The structures
of the ROCK1, ROCK2, HDAC1 and HDAC6 inhibitors with their pIC50 values were obtained
from the ChEMBL database. The dominant microspecies of all compounds at physiological
pH were selected by Marvin Sketch Sketch 6.1.0 program and their further geometrical
optimization were performed using the PM3 semi-empirical method and the Hartree-Fock
method with 3-21G basis set.
The virtual docking procedures for all four enzymes were validated and the calculated RMSD
values were below 2Å. The critical parts of the structures that establish the interactions
crucial for the inhibition of HDAC1, HDAC6, ROCK1, and ROCK2 were identified. Based on
the obtained resultsdual HDAC/ROCK inhibitors were designed and evaluated by validated
docking procedures and in silico ADMET profiling.
Taking into account all these findings, the most active compounds are selected and will be
further synthesized and evaluated using in vitro enzyme and cell tests.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Virtual docking and design of novel Histone deacetylase and Rho- associated protein kinases dual inhibitors (HDAC/ROCKs)
SP  - 46
EP  - 46
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5005
ER  - 

@conference{
author = "Beljkaš, Milan and Petković, Miloš and Nikolić, Katarina and Oljačić, Slavica",
year = "2023",
abstract = "Histone deacetylases (HDACs) belong to a family of epigenetic enzymes that has 18 different
isoforms and play an important role in the development and progression of various tumors.
To date, five histone deacetylase inhibitors have been approved by the FDA, and are used
to treat multiple myeloma, cutaneous T-cell lymphoma, peripheral T-cell lymphoma, and
breast cancer (estrogen and/or progesterone positive) [1]. All of them are non-selective.
Therefore, their safety profile is poor and their efficacy is low in single therapy. One of our
previous research projects demonstrated the synergistic effect of HDAC inhibitors and
inhibitors of Rho-associated protein kinases (ROCK) in the treatment of pancreatic ductal
adenocarcinoma (PDAC) [2]. This finding led us to design of the dual HDAC/ROCK inhibitors
with potential effects on PDAC by using structure-based molecular docking method.
Molecular docking study was performed using GOLD software. The crystal structures of
ROCK1 (PDB: 6E9W), ROCK2 (PDB: 7JNT), HDAC1 (PDB: 5ICN), and HDAC6 (PDB: 5EDU)
enzymes were downloaded from the Protein Data Bank (PDB). The enzymes were prepared
for docking study using the online software Play Molecule-ProteinPrepare. The structures
of the ROCK1, ROCK2, HDAC1 and HDAC6 inhibitors with their pIC50 values were obtained
from the ChEMBL database. The dominant microspecies of all compounds at physiological
pH were selected by Marvin Sketch Sketch 6.1.0 program and their further geometrical
optimization were performed using the PM3 semi-empirical method and the Hartree-Fock
method with 3-21G basis set.
The virtual docking procedures for all four enzymes were validated and the calculated RMSD
values were below 2Å. The critical parts of the structures that establish the interactions
crucial for the inhibition of HDAC1, HDAC6, ROCK1, and ROCK2 were identified. Based on
the obtained resultsdual HDAC/ROCK inhibitors were designed and evaluated by validated
docking procedures and in silico ADMET profiling.
Taking into account all these findings, the most active compounds are selected and will be
further synthesized and evaluated using in vitro enzyme and cell tests.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Virtual docking and design of novel Histone deacetylase and Rho- associated protein kinases dual inhibitors (HDAC/ROCKs)",
pages = "46-46",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5005"
}

Beljkaš, M., Petković, M., Nikolić, K.,& Oljačić, S.. (2023). Virtual docking and design of novel Histone deacetylase and Rho- associated protein kinases dual inhibitors (HDAC/ROCKs). in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 46-46.
https://hdl.handle.net/21.15107/rcub_farfar_5005

Beljkaš M, Petković M, Nikolić K, Oljačić S. Virtual docking and design of novel Histone deacetylase and Rho- associated protein kinases dual inhibitors (HDAC/ROCKs). in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:46-46.
https://hdl.handle.net/21.15107/rcub_farfar_5005 .

Beljkaš, Milan, Petković, Miloš, Nikolić, Katarina, Oljačić, Slavica, "Virtual docking and design of novel Histone deacetylase and Rho- associated protein kinases dual inhibitors (HDAC/ROCKs)" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):46-46,
https://hdl.handle.net/21.15107/rcub_farfar_5005 .

TY  - JOUR
AU  - Jovanović, Milan
AU  - Nikolić, Katarina
AU  - Čarapić, Marija
AU  - Aleksić, Mara
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4931
AB  - A comprehensive investigation of tyrosine kinase inhibitor erlotinib (ERL) electrochemical behavior and interaction with DNA was performed with the aim to clarify its redox mechanism and to determine the mode of binding. Irreversible oxidation and reduction processes of ERL on glassy carbon electrode were investigated using three voltammetric techniques CV, DPV, SWV in pH range between 2.0 and 9.0. Oxidation was established as an adsorption-controlled process, while the reduction manifested diffusion-adsorption mixed controlled process in acidic medium and adsorption became predominant in the neutral solutions. According to the determined number of transferred electrons and protons, oxidation and reduction mechanism of ERL are proposed. To follow the interaction between ERL and DNA, the multilayer ct-DNA electrochemical biosensor was incubated in ERL solutions concentrations ranged from 2 × 10–7 M to 5 × 10–5 M (pH 4.6) for 30 min. SWV measurements have shown the decrease in deoxyadenosine peak current as a consequence of ERL increased concentration and binding to ct-DNA. The calculated value of binding constant was K = 8.25 × 104 M−1. Molecular docking showed that ERL forms hydrophobic interactions when docked into minor groove, as well as when intercalated, and molecular dynamics analysis predicted the stability of obtained complexes. These results together with voltammetric studies imply that the intercalation could be more dominant way ERL binding to DNA compared to minor groove binding.
PB  - Elsevier B.V.
T2  - Journal of Pharmaceutical and Biomedical Analysis
T1  - Electrochemical and theoretical study on interaction between erlotinib and DNA
VL  - 234
DO  - 10.1016/j.jpba.2023.115560
ER  - 

@article{
author = "Jovanović, Milan and Nikolić, Katarina and Čarapić, Marija and Aleksić, Mara",
year = "2023",
abstract = "A comprehensive investigation of tyrosine kinase inhibitor erlotinib (ERL) electrochemical behavior and interaction with DNA was performed with the aim to clarify its redox mechanism and to determine the mode of binding. Irreversible oxidation and reduction processes of ERL on glassy carbon electrode were investigated using three voltammetric techniques CV, DPV, SWV in pH range between 2.0 and 9.0. Oxidation was established as an adsorption-controlled process, while the reduction manifested diffusion-adsorption mixed controlled process in acidic medium and adsorption became predominant in the neutral solutions. According to the determined number of transferred electrons and protons, oxidation and reduction mechanism of ERL are proposed. To follow the interaction between ERL and DNA, the multilayer ct-DNA electrochemical biosensor was incubated in ERL solutions concentrations ranged from 2 × 10–7 M to 5 × 10–5 M (pH 4.6) for 30 min. SWV measurements have shown the decrease in deoxyadenosine peak current as a consequence of ERL increased concentration and binding to ct-DNA. The calculated value of binding constant was K = 8.25 × 104 M−1. Molecular docking showed that ERL forms hydrophobic interactions when docked into minor groove, as well as when intercalated, and molecular dynamics analysis predicted the stability of obtained complexes. These results together with voltammetric studies imply that the intercalation could be more dominant way ERL binding to DNA compared to minor groove binding.",
publisher = "Elsevier B.V.",
journal = "Journal of Pharmaceutical and Biomedical Analysis",
title = "Electrochemical and theoretical study on interaction between erlotinib and DNA",
volume = "234",
doi = "10.1016/j.jpba.2023.115560"
}

Jovanović, M., Nikolić, K., Čarapić, M.,& Aleksić, M.. (2023). Electrochemical and theoretical study on interaction between erlotinib and DNA. in Journal of Pharmaceutical and Biomedical Analysis
Elsevier B.V.., 234.
https://doi.org/10.1016/j.jpba.2023.115560

Jovanović M, Nikolić K, Čarapić M, Aleksić M. Electrochemical and theoretical study on interaction between erlotinib and DNA. in Journal of Pharmaceutical and Biomedical Analysis. 2023;234.
doi:10.1016/j.jpba.2023.115560 .

Jovanović, Milan, Nikolić, Katarina, Čarapić, Marija, Aleksić, Mara, "Electrochemical and theoretical study on interaction between erlotinib and DNA" in Journal of Pharmaceutical and Biomedical Analysis, 234 (2023),
https://doi.org/10.1016/j.jpba.2023.115560 . .

TY  - CONF
AU  - Borrello, Maria Teresa
AU  - Ružić, Dušan
AU  - Oakley, Fiona
AU  - Nikolić, Katarina
AU  - Mann, Jelena
AU  - Mann, Derek
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4912
PB  - Elsevire
C3  - Journal of Hepatology
T1  - Discovery of novel small molecule inhibitors of HDAC6 that suppress liver fibrosis
VL  - 78
IS  - S1
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4912
ER  - 

@conference{
author = "Borrello, Maria Teresa and Ružić, Dušan and Oakley, Fiona and Nikolić, Katarina and Mann, Jelena and Mann, Derek",
year = "2023",
publisher = "Elsevire",
journal = "Journal of Hepatology",
title = "Discovery of novel small molecule inhibitors of HDAC6 that suppress liver fibrosis",
volume = "78",
number = "S1",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4912"
}

Borrello, M. T., Ružić, D., Oakley, F., Nikolić, K., Mann, J.,& Mann, D.. (2023). Discovery of novel small molecule inhibitors of HDAC6 that suppress liver fibrosis. in Journal of Hepatology
Elsevire., 78(S1).
https://hdl.handle.net/21.15107/rcub_farfar_4912

Borrello MT, Ružić D, Oakley F, Nikolić K, Mann J, Mann D. Discovery of novel small molecule inhibitors of HDAC6 that suppress liver fibrosis. in Journal of Hepatology. 2023;78(S1).
https://hdl.handle.net/21.15107/rcub_farfar_4912 .

Borrello, Maria Teresa, Ružić, Dušan, Oakley, Fiona, Nikolić, Katarina, Mann, Jelena, Mann, Derek, "Discovery of novel small molecule inhibitors of HDAC6 that suppress liver fibrosis" in Journal of Hepatology, 78, no. S1 (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4912 .

TY  - CONF
AU  - Đoković, Nemanja
AU  - Ilić, Aleksandra
AU  - Čebzan, Alen
AU  - Radović, Branko
AU  - Ružić, Dušan
AU  - Đurić, Ana
AU  - Srdić-Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5001
AB  - Pancreatic ductal adenocarcinoma (PDAC) ranks among the most formidable and deadly
types of cancer. The emergence of chemoresistance in PDAC plays a significant role in the
unfavorable survival rates, making it imperative to swiftly develop new pharmaceutical
strategies to address this issue and improve treatment outcomes for PDAC (1). Considering
the numerous epigenetic changes observed in PDAC, the utilization of epigenetic drugs,
such as histone deacetylase (HDAC) inhibitors, holds a great promise as a transformative
approach, particularly when used in combination therapy settings (2).
In this study, we investigated the potential of utilizing drug sensitivity data and the basal
gene expression of pancreatic carcinoma cell lines to develop a bioinformatics screening
protocol for prediction of the combinatorial options available for HDAC inhibitors, including
sirtuin (SIRT) inhibitors. Experimental validation of the protocol performed on the two
pancreatic carcinoma cell lines (MIA PaCa-2 cells and PANC-1) confirmed the identified
synergisms between HDAC inhibitors and sphingosine 1-phosphate (S1P) receptor agonist
– fingolimod, or HDAC inhibitors and Rho-associated protein kinase (ROCK) inhibitor – RKI1447 (3).
Developed bioinformatics screening protocol for predictions of synergistic drug
combinations in PDAC identified several previously unreported interaction partners of
HDAC inhibitors. Predicted interaction partners of HDAC inhibitors including Aurora Kinase
A (AURKA) inhibitor, glutaminase (GLS) inhibitor and WEE1 kinase inhibitor were selected
for the design of novel classes of dual-acting HDAC inhibitors by the means of structure-based molecular modelling. Novel dual inhibitors (SIRT/AURKA, HDAC/GLS and HDAC/WEE1)
were designed relying on the known pharmacophoric features and molecular docking
models developed for each of the targets of interest. The docking scores of the designed
inhibitors revealed a notable affinity towards the specific targets. Additionally, when
combined with predictions of drug synergy, these designed molecules exhibit great
potential as promising structures for subsequent experimental evaluation.
PB  - International Association of Physical Chemists
C3  - 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
T1  - Towards the multitarget HDAC Inhibitors for the treatment of pancreatic carcinoma by joining the drug synergy predictions and the molecular modeling
SP  - 47
EP  - 47
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5001
ER  - 

@conference{
author = "Đoković, Nemanja and Ilić, Aleksandra and Čebzan, Alen and Radović, Branko and Ružić, Dušan and Đurić, Ana and Srdić-Rajić, Tatjana and Nikolić, Katarina",
year = "2023",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) ranks among the most formidable and deadly
types of cancer. The emergence of chemoresistance in PDAC plays a significant role in the
unfavorable survival rates, making it imperative to swiftly develop new pharmaceutical
strategies to address this issue and improve treatment outcomes for PDAC (1). Considering
the numerous epigenetic changes observed in PDAC, the utilization of epigenetic drugs,
such as histone deacetylase (HDAC) inhibitors, holds a great promise as a transformative
approach, particularly when used in combination therapy settings (2).
In this study, we investigated the potential of utilizing drug sensitivity data and the basal
gene expression of pancreatic carcinoma cell lines to develop a bioinformatics screening
protocol for prediction of the combinatorial options available for HDAC inhibitors, including
sirtuin (SIRT) inhibitors. Experimental validation of the protocol performed on the two
pancreatic carcinoma cell lines (MIA PaCa-2 cells and PANC-1) confirmed the identified
synergisms between HDAC inhibitors and sphingosine 1-phosphate (S1P) receptor agonist
– fingolimod, or HDAC inhibitors and Rho-associated protein kinase (ROCK) inhibitor – RKI1447 (3).
Developed bioinformatics screening protocol for predictions of synergistic drug
combinations in PDAC identified several previously unreported interaction partners of
HDAC inhibitors. Predicted interaction partners of HDAC inhibitors including Aurora Kinase
A (AURKA) inhibitor, glutaminase (GLS) inhibitor and WEE1 kinase inhibitor were selected
for the design of novel classes of dual-acting HDAC inhibitors by the means of structure-based molecular modelling. Novel dual inhibitors (SIRT/AURKA, HDAC/GLS and HDAC/WEE1)
were designed relying on the known pharmacophoric features and molecular docking
models developed for each of the targets of interest. The docking scores of the designed
inhibitors revealed a notable affinity towards the specific targets. Additionally, when
combined with predictions of drug synergy, these designed molecules exhibit great
potential as promising structures for subsequent experimental evaluation.",
publisher = "International Association of Physical Chemists",
journal = "10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6",
title = "Towards the multitarget HDAC Inhibitors for the treatment of pancreatic carcinoma by joining the drug synergy predictions and the molecular modeling",
pages = "47-47",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5001"
}

Đoković, N., Ilić, A., Čebzan, A., Radović, B., Ružić, D., Đurić, A., Srdić-Rajić, T.,& Nikolić, K.. (2023). Towards the multitarget HDAC Inhibitors for the treatment of pancreatic carcinoma by joining the drug synergy predictions and the molecular modeling. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6
International Association of Physical Chemists., 47-47.
https://hdl.handle.net/21.15107/rcub_farfar_5001

Đoković N, Ilić A, Čebzan A, Radović B, Ružić D, Đurić A, Srdić-Rajić T, Nikolić K. Towards the multitarget HDAC Inhibitors for the treatment of pancreatic carcinoma by joining the drug synergy predictions and the molecular modeling. in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6. 2023;:47-47.
https://hdl.handle.net/21.15107/rcub_farfar_5001 .

Đoković, Nemanja, Ilić, Aleksandra, Čebzan, Alen, Radović, Branko, Ružić, Dušan, Đurić, Ana, Srdić-Rajić, Tatjana, Nikolić, Katarina, "Towards the multitarget HDAC Inhibitors for the treatment of pancreatic carcinoma by joining the drug synergy predictions and the molecular modeling" in 10th IAPC Meeting Tenth World Conference on Physico-Chemical Methods in Drug Discovery & Sixth World Conference on ADMET and DMPK Belgrade, Serbia, September 4-6 (2023):47-47,
https://hdl.handle.net/21.15107/rcub_farfar_5001 .

TY  - JOUR
AU  - Zhang, Lei
AU  - Xie, Xiulan
AU  - Đoković, Nemanja
AU  - Nikolić, Katarina
AU  - Kosenkov, Dmitri
AU  - Abendroth, Frank
AU  - Vázquez, Olalla
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4913
AB  - Dynamics are intrinsic to both RNA function and
structure. Yet, the available means to precisely provide RNA-based
processes with spatiotemporal resolution are scarce. Here, our
work pioneers a reversible approach to regulate RNA splicing
within primary patient-derived cells by synthetic photoswitches.
Our small molecule enables conditional real-time control at mRNA
and protein levels. NMR experiments, together with theoretical
calculations, photochemical characterization, fluorescence polarization
measurements, and living cell-based assays, confirmed lightdependent
exon inclusion as well as an increase in the target
functional protein. Therefore, we first demonstrated the potential
of photopharmacology modulation in splicing, tweaking the
current optochemical toolkit. The timeliness on the consolidation
of RNA research as the driving force toward therapeutical innovation holds the promise that our approach will contribute to
redrawing the vision of RNA.
PB  - American Chemical Society
T2  - Journal of the American Chemical Society
T1  - Reversible Control of RNA Splicing by Photoswitchable Small Molecules
VL  - 145
IS  - 23
SP  - 12783
EP  - 12792
DO  - 10.1021/jacs.3c03275
ER  - 

@article{
author = "Zhang, Lei and Xie, Xiulan and Đoković, Nemanja and Nikolić, Katarina and Kosenkov, Dmitri and Abendroth, Frank and Vázquez, Olalla",
year = "2023",
abstract = "Dynamics are intrinsic to both RNA function and
structure. Yet, the available means to precisely provide RNA-based
processes with spatiotemporal resolution are scarce. Here, our
work pioneers a reversible approach to regulate RNA splicing
within primary patient-derived cells by synthetic photoswitches.
Our small molecule enables conditional real-time control at mRNA
and protein levels. NMR experiments, together with theoretical
calculations, photochemical characterization, fluorescence polarization
measurements, and living cell-based assays, confirmed lightdependent
exon inclusion as well as an increase in the target
functional protein. Therefore, we first demonstrated the potential
of photopharmacology modulation in splicing, tweaking the
current optochemical toolkit. The timeliness on the consolidation
of RNA research as the driving force toward therapeutical innovation holds the promise that our approach will contribute to
redrawing the vision of RNA.",
publisher = "American Chemical Society",
journal = "Journal of the American Chemical Society",
title = "Reversible Control of RNA Splicing by Photoswitchable Small Molecules",
volume = "145",
number = "23",
pages = "12783-12792",
doi = "10.1021/jacs.3c03275"
}

Zhang, L., Xie, X., Đoković, N., Nikolić, K., Kosenkov, D., Abendroth, F.,& Vázquez, O.. (2023). Reversible Control of RNA Splicing by Photoswitchable Small Molecules. in Journal of the American Chemical Society
American Chemical Society., 145(23), 12783-12792.
https://doi.org/10.1021/jacs.3c03275

Zhang L, Xie X, Đoković N, Nikolić K, Kosenkov D, Abendroth F, Vázquez O. Reversible Control of RNA Splicing by Photoswitchable Small Molecules. in Journal of the American Chemical Society. 2023;145(23):12783-12792.
doi:10.1021/jacs.3c03275 .

Zhang, Lei, Xie, Xiulan, Đoković, Nemanja, Nikolić, Katarina, Kosenkov, Dmitri, Abendroth, Frank, Vázquez, Olalla, "Reversible Control of RNA Splicing by Photoswitchable Small Molecules" in Journal of the American Chemical Society, 145, no. 23 (2023):12783-12792,
https://doi.org/10.1021/jacs.3c03275 . .

TY  - JOUR
AU  - Dokmanović, Jelena
AU  - Kasagić-Vujanović, Irena
AU  - Gagić, Žarko
AU  - Nikolić, Katarina
AU  - Čarapić, Marija
AU  - Agbaba, Danica
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4474
AB  - Using the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5-methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min-1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15-35 μg mL-1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs.
PB  - Akademiai Kiado ZRt.
T2  - Acta Chromatographica
T1  - Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities
DO  - 10.1556/1326.2022.01111
ER  - 

@article{
author = "Dokmanović, Jelena and Kasagić-Vujanović, Irena and Gagić, Žarko and Nikolić, Katarina and Čarapić, Marija and Agbaba, Danica",
year = "2023",
abstract = "Using the Design of Experiments methodology (Response-Surface Methodology and Derringer's Desirability Function), a simple, fast and robust RP-HPLC method was developed for the analysis of enrofloxacin (EFC), its impurity A (fluoroquinolonic acid, FQ) and impurity B (ciprofloxacin, CPX). Gradient elution of samples was performed on a Zorbax Eclipse XDB C18 column (150 × 4.6 mm, 3.5 μm) with a mobile phase consisting of 32 mM phosphate buffer pH 3.5-methanol (0 min-19.6% methanol; 15.5 min-19.6% methanol; 29.5 min-80% methanol; 30 min-19.6% methanol; 35 min-19.6% methanol), delivered at a flow rate of 1.5 mL min-1, wavelength of detection 278 nm (for EFX and CFX) and 265 nm for FQ. A good linear response was achieved in the range 15-35 μg mL-1 (EFX) and LOQ-150% for impurities (CFX and FQ). Other validation parameters were also tested: precision, accuracy, sensitivity and robustness. The developed method was shown to be simple, practical and suitable for the analysis of EFC and its impurities (CPX, FQ) in veterinary drugs.",
publisher = "Akademiai Kiado ZRt.",
journal = "Acta Chromatographica",
title = "Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities",
doi = "10.1556/1326.2022.01111"
}

Dokmanović, J., Kasagić-Vujanović, I., Gagić, Ž., Nikolić, K., Čarapić, M.,& Agbaba, D.. (2023). Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities. in Acta Chromatographica
Akademiai Kiado ZRt...
https://doi.org/10.1556/1326.2022.01111

Dokmanović J, Kasagić-Vujanović I, Gagić Ž, Nikolić K, Čarapić M, Agbaba D. Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities. in Acta Chromatographica. 2023;.
doi:10.1556/1326.2022.01111 .

Dokmanović, Jelena, Kasagić-Vujanović, Irena, Gagić, Žarko, Nikolić, Katarina, Čarapić, Marija, Agbaba, Danica, "Design of experiments and Derringer's desirability function in optimisation and validation of RP-HPLC method for the analysis of enrofloxacin and its impurities" in Acta Chromatographica (2023),
https://doi.org/10.1556/1326.2022.01111 . .

TY  - JOUR
AU  - Đoković, Nemanja
AU  - Đurić, Ana
AU  - Ružić, Dušan
AU  - Srdić-Rajić, Tatjana
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4472
AB  - Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Development of the chemoresistance in the PDAC is one of the key contributors to the poor survival outcomes and the major reason for urgent development of novel pharmacological approaches in a treatment of PDAC. Systematically tailored combination therapy holds the promise for advancing the treatment of PDAC. However, the number of possible combinations of pharmacological agents is too large to be explored experimentally. In respect to the many epigenetic alterations in PDAC, epigenetic drugs including histone deacetylase inhibitors (HDACi) could be seen as the game changers especially in combined therapy settings. In this work, we explored a possibility of using drug-sensitivity data together with the basal gene expression of pancreatic cell lines to predict combinatorial options available for HDACi. Developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC identified the sphingolipid signaling pathway with associated downstream effectors as a promising novel targets for future development of multi-target therapeutics or combined therapy with HDACi. Through the experimental validation, we have characterized novel synergism between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, and between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma
VL  - 16
IS  - 2
DO  - 10.3390/ph16020294
ER  - 

@article{
author = "Đoković, Nemanja and Đurić, Ana and Ružić, Dušan and Srdić-Rajić, Tatjana and Nikolić, Katarina",
year = "2023",
abstract = "Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and lethal malignancies. Development of the chemoresistance in the PDAC is one of the key contributors to the poor survival outcomes and the major reason for urgent development of novel pharmacological approaches in a treatment of PDAC. Systematically tailored combination therapy holds the promise for advancing the treatment of PDAC. However, the number of possible combinations of pharmacological agents is too large to be explored experimentally. In respect to the many epigenetic alterations in PDAC, epigenetic drugs including histone deacetylase inhibitors (HDACi) could be seen as the game changers especially in combined therapy settings. In this work, we explored a possibility of using drug-sensitivity data together with the basal gene expression of pancreatic cell lines to predict combinatorial options available for HDACi. Developed bioinformatics screening protocol for predictions of synergistic drug combinations in PDAC identified the sphingolipid signaling pathway with associated downstream effectors as a promising novel targets for future development of multi-target therapeutics or combined therapy with HDACi. Through the experimental validation, we have characterized novel synergism between HDACi and a Rho-associated protein kinase (ROCK) inhibitor RKI-1447, and between HDACi and a sphingosine 1-phosphate (S1P) receptor agonist fingolimod.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma",
volume = "16",
number = "2",
doi = "10.3390/ph16020294"
}

Đoković, N., Đurić, A., Ružić, D., Srdić-Rajić, T.,& Nikolić, K.. (2023). Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma. in Pharmaceuticals
MDPI., 16(2).
https://doi.org/10.3390/ph16020294

Đoković N, Đurić A, Ružić D, Srdić-Rajić T, Nikolić K. Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma. in Pharmaceuticals. 2023;16(2).
doi:10.3390/ph16020294 .

Đoković, Nemanja, Đurić, Ana, Ružić, Dušan, Srdić-Rajić, Tatjana, Nikolić, Katarina, "Correlating Basal Gene Expression across Chemical Sensitivity Data to Screen for Novel Synergistic Interactors of HDAC Inhibitors in Pancreatic Carcinoma" in Pharmaceuticals, 16, no. 2 (2023),
https://doi.org/10.3390/ph16020294 . .

TY  - JOUR
AU  - Đoković, Nemanja
AU  - Rahnasto-Rilla, Minna
AU  - Lougiakis, Nikolas
AU  - Lahtela-Kakkonen, Maija
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4416
AB  - A growing body of preclinical evidence recognized selective sirtuin 2 (SIRT2) inhibitors as novel therapeutics for treatment of age-related diseases. However, none of the SIRT2 inhibitors have reached clinical trials yet. Transformative potential of machine learning (ML) in early stages of drug discovery has been witnessed by widespread adoption of these techniques in recent years. Despite great potential, there is a lack of robust and large-scale ML models for discovery of novel SIRT2 inhibitors. In order to support virtual screening (VS), lead optimization, or facilitate the selection of SIRT2 inhibitors for experimental evaluation, a machine-learning-based tool titled SIRT2i_Predictor was developed. The tool was built on a panel of high-quality ML regression and classification-based models for prediction of inhibitor potency and SIRT1-3 isoform selectivity. State-of-the-art ML algorithms were used to train the models on a large and diverse dataset containing 1797 compounds. Benchmarking against structure-based VS protocol indicated comparable coverage of chemical space with great gain in speed. The tool was applied to screen the in-house database of compounds, corroborating the utility in the prioritization of compounds for costly in vitro screening campaigns. The easy-to-use web-based interface makes SIRT2i_Predictor a convenient tool for the wider community. The SIRT2i_Predictor’s source code is made available online.
PB  - MDPI
T2  - Pharmaceuticals
T1  - SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors
VL  - 16
IS  - 1
DO  - 10.3390/ph16010127
ER  - 

@article{
author = "Đoković, Nemanja and Rahnasto-Rilla, Minna and Lougiakis, Nikolas and Lahtela-Kakkonen, Maija and Nikolić, Katarina",
year = "2023",
abstract = "A growing body of preclinical evidence recognized selective sirtuin 2 (SIRT2) inhibitors as novel therapeutics for treatment of age-related diseases. However, none of the SIRT2 inhibitors have reached clinical trials yet. Transformative potential of machine learning (ML) in early stages of drug discovery has been witnessed by widespread adoption of these techniques in recent years. Despite great potential, there is a lack of robust and large-scale ML models for discovery of novel SIRT2 inhibitors. In order to support virtual screening (VS), lead optimization, or facilitate the selection of SIRT2 inhibitors for experimental evaluation, a machine-learning-based tool titled SIRT2i_Predictor was developed. The tool was built on a panel of high-quality ML regression and classification-based models for prediction of inhibitor potency and SIRT1-3 isoform selectivity. State-of-the-art ML algorithms were used to train the models on a large and diverse dataset containing 1797 compounds. Benchmarking against structure-based VS protocol indicated comparable coverage of chemical space with great gain in speed. The tool was applied to screen the in-house database of compounds, corroborating the utility in the prioritization of compounds for costly in vitro screening campaigns. The easy-to-use web-based interface makes SIRT2i_Predictor a convenient tool for the wider community. The SIRT2i_Predictor’s source code is made available online.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors",
volume = "16",
number = "1",
doi = "10.3390/ph16010127"
}

Đoković, N., Rahnasto-Rilla, M., Lougiakis, N., Lahtela-Kakkonen, M.,& Nikolić, K.. (2023). SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors. in Pharmaceuticals
MDPI., 16(1).
https://doi.org/10.3390/ph16010127

Đoković N, Rahnasto-Rilla M, Lougiakis N, Lahtela-Kakkonen M, Nikolić K. SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors. in Pharmaceuticals. 2023;16(1).
doi:10.3390/ph16010127 .

Đoković, Nemanja, Rahnasto-Rilla, Minna, Lougiakis, Nikolas, Lahtela-Kakkonen, Maija, Nikolić, Katarina, "SIRT2i_Predictor: A Machine Learning-Based Tool to Facilitate the Discovery of Novel SIRT2 Inhibitors" in Pharmaceuticals, 16, no. 1 (2023),
https://doi.org/10.3390/ph16010127 . .

TY  - CONF
AU  - Čebzan, Alen
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4952
PB  - European Association for Cancer Research
C3  - EACR-Boehringer Ingelheim Drugging and Regulating the MAP Kinase Pathway Virtual Event, Worldwide : 21 - 22 February 2023
T1  - Computer-aided drug design of MAPK inhibitors by combined 3D-QSAR analysis and molecular docking
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4952
ER  - 

@conference{
author = "Čebzan, Alen and Ružić, Dušan and Nikolić, Katarina",
year = "2023",
publisher = "European Association for Cancer Research",
journal = "EACR-Boehringer Ingelheim Drugging and Regulating the MAP Kinase Pathway Virtual Event, Worldwide : 21 - 22 February 2023",
title = "Computer-aided drug design of MAPK inhibitors by combined 3D-QSAR analysis and molecular docking",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4952"
}

Čebzan, A., Ružić, D.,& Nikolić, K.. (2023). Computer-aided drug design of MAPK inhibitors by combined 3D-QSAR analysis and molecular docking. in EACR-Boehringer Ingelheim Drugging and Regulating the MAP Kinase Pathway Virtual Event, Worldwide : 21 - 22 February 2023
European Association for Cancer Research..
https://hdl.handle.net/21.15107/rcub_farfar_4952

Čebzan A, Ružić D, Nikolić K. Computer-aided drug design of MAPK inhibitors by combined 3D-QSAR analysis and molecular docking. in EACR-Boehringer Ingelheim Drugging and Regulating the MAP Kinase Pathway Virtual Event, Worldwide : 21 - 22 February 2023. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_4952 .

Čebzan, Alen, Ružić, Dušan, Nikolić, Katarina, "Computer-aided drug design of MAPK inhibitors by combined 3D-QSAR analysis and molecular docking" in EACR-Boehringer Ingelheim Drugging and Regulating the MAP Kinase Pathway Virtual Event, Worldwide : 21 - 22 February 2023 (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4952 .

TY  - CONF
AU  - Nikolić, Katarina
AU  - Radan, Milica
AU  - Đikić, Teodora
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4762
PB  - European Research Network on Signal Transduction CA18133 (ERNEST)
C3  - 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece
T1  - Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders
SP  - 125
EP  - 125
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4762
ER  - 

@conference{
author = "Nikolić, Katarina and Radan, Milica and Đikić, Teodora",
year = "2023",
publisher = "European Research Network on Signal Transduction CA18133 (ERNEST)",
journal = "8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece",
title = "Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders",
pages = "125-125",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4762"
}

Nikolić, K., Radan, M.,& Đikić, T.. (2023). Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders. in 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece
European Research Network on Signal Transduction CA18133 (ERNEST)., 125-125.
https://hdl.handle.net/21.15107/rcub_farfar_4762

Nikolić K, Radan M, Đikić T. Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders. in 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece. 2023;:125-125.
https://hdl.handle.net/21.15107/rcub_farfar_4762 .

Nikolić, Katarina, Radan, Milica, Đikić, Teodora, "Polypharmacological strategy in rational drug design of new dual 5HT2A/D2-R antagonists as potentially effective therapeutics of complex neurological and mental disorders" in 8th and final ERNEST Meeting "GPCR structure and function: The present and perspectives for the future”, May 3-7, 2023 in Crete, Greece (2023):125-125,
https://hdl.handle.net/21.15107/rcub_farfar_4762 .

TY  - CONF
AU  - Sánchez-Martín, Victoria
AU  - Ružić, Dušan
AU  - Castilla-Maldonado, Ignacio
AU  - Ortiz-González, Matilde
AU  - Soriano-Lerma, Ana
AU  - Linde-Rodríguez, Ángel
AU  - Pérez-Carrasco, Virginia
AU  - Ramirez-Macias, Inmaculada
AU  - Soriano, Miguel
AU  - Nikolić, Katarina
AU  - García-Salcedo, Jose Antonio
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4911
AB  - Metastasis is a major problem in the management of cancer, remaining as the principal cause of cancer death. Despite recent advances, treatment options are still limited. Naphthalimide (1H-benzo[de]isoquinoline-1,3-(2H)-dione) analogs have been considered as promising anticancer agents against different tumor types. However, antimetastatic potential of naphthalimides has not been previously established. The aim of this work was to evaluate the possible antimetastatic activ-ity of a panel of 21 naphthalimides which were synthesized in the laboratory. We studied the inhib-itory effects of these compounds on cancer proliferation, clonogenicity and cell cycle progression. We identified 5 naphthalimides with a potent and selective inhibition of growth in SW620 metastatic cells compared to CRL1790 non-tumoral ones. In addition, these 5 naphthalimides induced a sig-nificant arrest at S and G2/M phase in SW620 cells. Finally, we selected the leading compound 20B, which inhibited clonogenic expansion in SW620 cells even at 10 μM. These results shed light on 20B naphthalimide as an emerging antimetastatic agent. Future studies are required to determine its mechanism of action.
PB  - MDPI
C3  - Medical sciences forum
T1  - Screening of naphthalimides as antimetastatic agents
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4911
ER  - 

@conference{
author = "Sánchez-Martín, Victoria and Ružić, Dušan and Castilla-Maldonado, Ignacio and Ortiz-González, Matilde and Soriano-Lerma, Ana and Linde-Rodríguez, Ángel and Pérez-Carrasco, Virginia and Ramirez-Macias, Inmaculada and Soriano, Miguel and Nikolić, Katarina and García-Salcedo, Jose Antonio",
year = "2023",
abstract = "Metastasis is a major problem in the management of cancer, remaining as the principal cause of cancer death. Despite recent advances, treatment options are still limited. Naphthalimide (1H-benzo[de]isoquinoline-1,3-(2H)-dione) analogs have been considered as promising anticancer agents against different tumor types. However, antimetastatic potential of naphthalimides has not been previously established. The aim of this work was to evaluate the possible antimetastatic activ-ity of a panel of 21 naphthalimides which were synthesized in the laboratory. We studied the inhib-itory effects of these compounds on cancer proliferation, clonogenicity and cell cycle progression. We identified 5 naphthalimides with a potent and selective inhibition of growth in SW620 metastatic cells compared to CRL1790 non-tumoral ones. In addition, these 5 naphthalimides induced a sig-nificant arrest at S and G2/M phase in SW620 cells. Finally, we selected the leading compound 20B, which inhibited clonogenic expansion in SW620 cells even at 10 μM. These results shed light on 20B naphthalimide as an emerging antimetastatic agent. Future studies are required to determine its mechanism of action.",
publisher = "MDPI",
journal = "Medical sciences forum",
title = "Screening of naphthalimides as antimetastatic agents",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4911"
}

Sánchez-Martín, V., Ružić, D., Castilla-Maldonado, I., Ortiz-González, M., Soriano-Lerma, A., Linde-Rodríguez, Á., Pérez-Carrasco, V., Ramirez-Macias, I., Soriano, M., Nikolić, K.,& García-Salcedo, J. A.. (2023). Screening of naphthalimides as antimetastatic agents. in Medical sciences forum
MDPI..
https://hdl.handle.net/21.15107/rcub_farfar_4911

Sánchez-Martín V, Ružić D, Castilla-Maldonado I, Ortiz-González M, Soriano-Lerma A, Linde-Rodríguez Á, Pérez-Carrasco V, Ramirez-Macias I, Soriano M, Nikolić K, García-Salcedo JA. Screening of naphthalimides as antimetastatic agents. in Medical sciences forum. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_4911 .

Sánchez-Martín, Victoria, Ružić, Dušan, Castilla-Maldonado, Ignacio, Ortiz-González, Matilde, Soriano-Lerma, Ana, Linde-Rodríguez, Ángel, Pérez-Carrasco, Virginia, Ramirez-Macias, Inmaculada, Soriano, Miguel, Nikolić, Katarina, García-Salcedo, Jose Antonio, "Screening of naphthalimides as antimetastatic agents" in Medical sciences forum (2023),
https://hdl.handle.net/21.15107/rcub_farfar_4911 .

TY  - CONF
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Ružić, Dušan
AU  - Nikolić, Katarina
AU  - Čudina, Olivera
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5451
AB  - Inflammation is a part of immune system's response to harmful intrinsic and
extrinsic stimuli, such as infection or injury. It has an important role in progression of some diseases, such as cancer, arthritis, stroke [1]. It is considered that inhibition of COX 2 and 5 LOX pathways of production of inflammation mediators provides a new strategy for development of more effective anticancer drugs [2]. The aim of this study was designing of novel COX 2/5 LOX inhibitors with improved activity towards both enzymes using quantitative structure activity relationships (QSAR). QSAR modeling was applied on a literature data set consisting of 28 dual COX 2/5 LOX inhibitors and obtained pharmacophoric features were used in design of novel compounds. Regarding prediction of activity of novel COX 2 and 5 LOX inhibitors, two models were developed. Based on values of Q2 (0.53 (COX 2 model) and 0.71 (5 LOX model)) and R2 pred (0.85 (for both COX 2 and 5 LOX models)), developed models have good predictive ability and can be used for activity prediction of novel designed compounds.
Obtained values of r2m, r'2m, and r ̅2m were higher than 0.5 and Δr2m was lower than 0.2 indicating high predictive quality of developed models. Applicability domain (AD) was defined using Leverage approach and all compounds were inside the AD. In order to get more potent dual inhibitors of COX 2 and 5 LOX enzymes, compounds with high pIC50 values were chosen for design of novel compounds. As a result, 32 novel compounds were designed and according to predicted pIC50 values can be considered promising dual COX 2 and 5 LOX inhibitors.
PB  - Institut Químic de Sarrià - Universitat Ramon Llull (IQS-URL)
C3  - MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts
T1  - Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis
SP  - 57
EP  - 57
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5451
ER  - 

@conference{
author = "Bošković, Jelena and Dobričić, Vladimir and Ružić, Dušan and Nikolić, Katarina and Čudina, Olivera",
year = "2022",
abstract = "Inflammation is a part of immune system's response to harmful intrinsic and
extrinsic stimuli, such as infection or injury. It has an important role in progression of some diseases, such as cancer, arthritis, stroke [1]. It is considered that inhibition of COX 2 and 5 LOX pathways of production of inflammation mediators provides a new strategy for development of more effective anticancer drugs [2]. The aim of this study was designing of novel COX 2/5 LOX inhibitors with improved activity towards both enzymes using quantitative structure activity relationships (QSAR). QSAR modeling was applied on a literature data set consisting of 28 dual COX 2/5 LOX inhibitors and obtained pharmacophoric features were used in design of novel compounds. Regarding prediction of activity of novel COX 2 and 5 LOX inhibitors, two models were developed. Based on values of Q2 (0.53 (COX 2 model) and 0.71 (5 LOX model)) and R2 pred (0.85 (for both COX 2 and 5 LOX models)), developed models have good predictive ability and can be used for activity prediction of novel designed compounds.
Obtained values of r2m, r'2m, and r ̅2m were higher than 0.5 and Δr2m was lower than 0.2 indicating high predictive quality of developed models. Applicability domain (AD) was defined using Leverage approach and all compounds were inside the AD. In order to get more potent dual inhibitors of COX 2 and 5 LOX enzymes, compounds with high pIC50 values were chosen for design of novel compounds. As a result, 32 novel compounds were designed and according to predicted pIC50 values can be considered promising dual COX 2 and 5 LOX inhibitors.",
publisher = "Institut Químic de Sarrià - Universitat Ramon Llull (IQS-URL)",
journal = "MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts",
title = "Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis",
pages = "57-57",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5451"
}

Bošković, J., Dobričić, V., Ružić, D., Nikolić, K.,& Čudina, O.. (2022). Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis. in MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts
Institut Químic de Sarrià - Universitat Ramon Llull (IQS-URL)., 57-57.
https://hdl.handle.net/21.15107/rcub_farfar_5451

Bošković J, Dobričić V, Ružić D, Nikolić K, Čudina O. Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis. in MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts. 2022;:57-57.
https://hdl.handle.net/21.15107/rcub_farfar_5451 .

Bošković, Jelena, Dobričić, Vladimir, Ružić, Dušan, Nikolić, Katarina, Čudina, Olivera, "Design of novel dual COX 2 and 5 LOX inhibitors using quantitative structure activity relationships analysis" in MedChem 2022, XI Paul Ehrlich Euro-PhD Network, Barcelona, July 14th - 16th 2022, Book of Abstracts (2022):57-57,
https://hdl.handle.net/21.15107/rcub_farfar_5451 .

TY  - JOUR
AU  - Bošković, Jelena
AU  - Ružić, Dušan
AU  - Čudina, Olivera
AU  - Nikolić, Katarina
AU  - Dobričić, Vladimir
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5442
AB  - Background: Inflammation is a critical component of many disease progressions, such as malignancy, cardiovascular and rheumatic diseases. The inhibition of inflammatory mediators synthesis by modulation of cyclooxygenase (COX) and lipoxygenase (LOX) pathways provides challenging strategy for development of more effective drugs.

Objective: The aim of this study was to design dual COX-2 and 5-LOX inhibitors with iron-chelating properties using a combination of ligand-based (three-dimensional quantitative structure-activity relationship (3D-QSAR)) and structure-based (molecular docking) methods..

Methods: The 3D-QSAR analysis was applied on a literature dataset consisting of 28 dual COX-2 and 5- LOX inhibitors in Pentacle software. The quality of developed COX-2 and 5-LOX 3D-QSAR models were evaluated by internal and external validation methods. The molecular docking analysis was performed in GOLD software, while selected ADMET properties were predicted in ADMET predictor software.

Results: According to the molecular docking studies, the class of sulfohydroxamic acid analogues, previously designed by 3D-QSAR, were clustered as potential dual COX-2 and 5-LOX inhibitors with ironchelating properties. Based on the 3D-QSAR and molecular docking, 1j, 1g and 1l were selected as the most promising dual COX-2 and 5-LOX inhibitors. According to the in silico ADMET predictions, all compounds had ADMET_Risk score less than 7 and CYP_Risk score lower than 2.5. Designed compounds were not estimated as hERG inhibitors and 1j had improved intrinsic solubility (8.704) in comparison to the dataset compounds (0.411-7.946).

Conclusion: By combining 3D-QSAR and molecular docking, three compounds (1j, 1g and 1l) were selected as the most promising designed dual COX-2 and 5-LOX inhibitors, for which good activity, as well as favourable ADMET properties and toxicity, are expected.
PB  - Bentham Science Publishers
T2  - Letters in Drug Design & Discovery
T1  - Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods
VL  - 19
IS  - 4
SP  - 279
EP  - 292
DO  - 10.2174/1570180818666210714161908
ER  - 

@article{
author = "Bošković, Jelena and Ružić, Dušan and Čudina, Olivera and Nikolić, Katarina and Dobričić, Vladimir",
year = "2022",
abstract = "Background: Inflammation is a critical component of many disease progressions, such as malignancy, cardiovascular and rheumatic diseases. The inhibition of inflammatory mediators synthesis by modulation of cyclooxygenase (COX) and lipoxygenase (LOX) pathways provides challenging strategy for development of more effective drugs.

Objective: The aim of this study was to design dual COX-2 and 5-LOX inhibitors with iron-chelating properties using a combination of ligand-based (three-dimensional quantitative structure-activity relationship (3D-QSAR)) and structure-based (molecular docking) methods..

Methods: The 3D-QSAR analysis was applied on a literature dataset consisting of 28 dual COX-2 and 5- LOX inhibitors in Pentacle software. The quality of developed COX-2 and 5-LOX 3D-QSAR models were evaluated by internal and external validation methods. The molecular docking analysis was performed in GOLD software, while selected ADMET properties were predicted in ADMET predictor software.

Results: According to the molecular docking studies, the class of sulfohydroxamic acid analogues, previously designed by 3D-QSAR, were clustered as potential dual COX-2 and 5-LOX inhibitors with ironchelating properties. Based on the 3D-QSAR and molecular docking, 1j, 1g and 1l were selected as the most promising dual COX-2 and 5-LOX inhibitors. According to the in silico ADMET predictions, all compounds had ADMET_Risk score less than 7 and CYP_Risk score lower than 2.5. Designed compounds were not estimated as hERG inhibitors and 1j had improved intrinsic solubility (8.704) in comparison to the dataset compounds (0.411-7.946).

Conclusion: By combining 3D-QSAR and molecular docking, three compounds (1j, 1g and 1l) were selected as the most promising designed dual COX-2 and 5-LOX inhibitors, for which good activity, as well as favourable ADMET properties and toxicity, are expected.",
publisher = "Bentham Science Publishers",
journal = "Letters in Drug Design & Discovery",
title = "Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods",
volume = "19",
number = "4",
pages = "279-292",
doi = "10.2174/1570180818666210714161908"
}

Bošković, J., Ružić, D., Čudina, O., Nikolić, K.,& Dobričić, V.. (2022). Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods. in Letters in Drug Design & Discovery
Bentham Science Publishers., 19(4), 279-292.
https://doi.org/10.2174/1570180818666210714161908

Bošković J, Ružić D, Čudina O, Nikolić K, Dobričić V. Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods. in Letters in Drug Design & Discovery. 2022;19(4):279-292.
doi:10.2174/1570180818666210714161908 .

Bošković, Jelena, Ružić, Dušan, Čudina, Olivera, Nikolić, Katarina, Dobričić, Vladimir, "Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods" in Letters in Drug Design & Discovery, 19, no. 4 (2022):279-292,
https://doi.org/10.2174/1570180818666210714161908 . .

TY  - GEN
AU  - Đoković, Nemanja
AU  - Ružić, Dušan
AU  - Rahnasto‐Rilla, Minna
AU  - Srdić Rajić, Tatjana
AU  - Lahtela-Kakkonen, Maija
AU  - Nikolić, Katarina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5462
AB  - Intricate structural heterogeneity of SIRT2
Initial goal: Discovery of novel scaffolds of SIRT2
inhibitors.
Experimentally confirmed conformal flexibility of SIRT2
binding site place it in the group of structures of
relatively challenging targets for modeling.
Different chemistry = Different conformational state
Scientific question: Have we discovered all states of
SIRT2?
Why deciphering of binding pocket dynamics is that
important from the aspect of structure-based drug
design?
T2  - Scientific Modeling Studies Serie, University of Eastern Finland, Kuopio, Finland, 16 May 2022
T1  - Expanding the Accessible Chemical Space of SIRT2 Inhibitors through Exploration of Binding Pocket Dynamics
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5462
ER  - 

@misc{
author = "Đoković, Nemanja and Ružić, Dušan and Rahnasto‐Rilla, Minna and Srdić Rajić, Tatjana and Lahtela-Kakkonen, Maija and Nikolić, Katarina",
year = "2022",
abstract = "Intricate structural heterogeneity of SIRT2
Initial goal: Discovery of novel scaffolds of SIRT2
inhibitors.
Experimentally confirmed conformal flexibility of SIRT2
binding site place it in the group of structures of
relatively challenging targets for modeling.
Different chemistry = Different conformational state
Scientific question: Have we discovered all states of
SIRT2?
Why deciphering of binding pocket dynamics is that
important from the aspect of structure-based drug
design?",
journal = "Scientific Modeling Studies Serie, University of Eastern Finland, Kuopio, Finland, 16 May 2022",
title = "Expanding the Accessible Chemical Space of SIRT2 Inhibitors through Exploration of Binding Pocket Dynamics",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5462"
}

Đoković, N., Ružić, D., Rahnasto‐Rilla, M., Srdić Rajić, T., Lahtela-Kakkonen, M.,& Nikolić, K.. (2022). Expanding the Accessible Chemical Space of SIRT2 Inhibitors through Exploration of Binding Pocket Dynamics. in Scientific Modeling Studies Serie, University of Eastern Finland, Kuopio, Finland, 16 May 2022.
https://hdl.handle.net/21.15107/rcub_farfar_5462

Đoković N, Ružić D, Rahnasto‐Rilla M, Srdić Rajić T, Lahtela-Kakkonen M, Nikolić K. Expanding the Accessible Chemical Space of SIRT2 Inhibitors through Exploration of Binding Pocket Dynamics. in Scientific Modeling Studies Serie, University of Eastern Finland, Kuopio, Finland, 16 May 2022. 2022;.
https://hdl.handle.net/21.15107/rcub_farfar_5462 .

Đoković, Nemanja, Ružić, Dušan, Rahnasto‐Rilla, Minna, Srdić Rajić, Tatjana, Lahtela-Kakkonen, Maija, Nikolić, Katarina, "Expanding the Accessible Chemical Space of SIRT2 Inhibitors through Exploration of Binding Pocket Dynamics" in Scientific Modeling Studies Serie, University of Eastern Finland, Kuopio, Finland, 16 May 2022 (2022),
https://hdl.handle.net/21.15107/rcub_farfar_5462 .