TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Nikolić, Miloš
AU  - Čanović, Petar
AU  - Zarić, Milan
AU  - Živković-Zarić, Radica
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Nikolić, Marina
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Dobričić, Vladimir
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5449
AB  - The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.
PB  - MDPI
T2  - Pharmaceutics
T1  - Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen
VL  - 16
IS  - 1
SP  - 1
DO  - 10.3390/pharmaceutics16010001
ER  - 

@article{
author = "Nedeljković, Nikola and Nikolić, Miloš and Čanović, Petar and Zarić, Milan and Živković-Zarić, Radica and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Nikolić, Marina and Jakovljević, Vladimir and Vujić, Zorica and Dobričić, Vladimir",
year = "2024",
abstract = "The objective of this study was to synthesize seven novel thiourea derivatives of naproxen (8–14), examine the anti-inflammatory activity of the newly synthesized compounds, investigate the cytotoxic potential of both sets of synthesized compounds (1–7 and 8–14), and select the most promising anti-inflammatory and antitumor drug candidates. The results of the in vivo anti-inflammatory study clearly showed that compounds 8 and 9 were capable of decreasing paw edema, as evident from a high percentage of inhibition (44.83% and 49.29%, respectively). In addition, the results of in vitro enzyme inhibition assays demonstrated that neither of the newly synthesized compounds reached 50% inhibition of 5-LOX at concentrations lower than 100 μM. In terms of antitumor potential, derivatives 3 and 8 exhibited strong cytotoxic effects on the HeLa cell line, suggesting the involvement of the extrinsic pathway of apoptosis. According to the overall results obtained for both sets of synthesized molecules, derivatives 4 and 8 can be underlined as molecules with the strongest anti-inflammatory activity, while derivatives 3 and 8 are the most promising cytotoxic agents.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen",
volume = "16",
number = "1",
pages = "1",
doi = "10.3390/pharmaceutics16010001"
}

Nedeljković, N., Nikolić, M., Čanović, P., Zarić, M., Živković-Zarić, R., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Nikolić, M., Jakovljević, V., Vujić, Z.,& Dobričić, V.. (2024). Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen. in Pharmaceutics
MDPI., 16(1), 1.
https://doi.org/10.3390/pharmaceutics16010001

Nedeljković N, Nikolić M, Čanović P, Zarić M, Živković-Zarić R, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Nikolić M, Jakovljević V, Vujić Z, Dobričić V. Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen. in Pharmaceutics. 2024;16(1):1.
doi:10.3390/pharmaceutics16010001 .

Nedeljković, Nikola, Nikolić, Miloš, Čanović, Petar, Zarić, Milan, Živković-Zarić, Radica, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Nikolić, Marina, Jakovljević, Vladimir, Vujić, Zorica, Dobričić, Vladimir, "Synthesis, Characterization, and Investigation of Anti-Inflammatory and Cytotoxic Activities of Novel Thiourea Derivatives of Naproxen" in Pharmaceutics, 16, no. 1 (2024):1,
https://doi.org/10.3390/pharmaceutics16010001 . .

TY  - JOUR
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Jeremić, Nevena
AU  - Novaković, Jovana
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4756
AB  - The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent
PB  - MDPI
T2  - Pharmaceuticals
T1  - Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen
VL  - 16
IS  - 5
DO  - 10.3390/ph16050666
ER  - 

@article{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Jeremić, Nevena and Novaković, Jovana and Jakovljević, Vladimir and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "The aim of the study was a synthesis and investigation of the dose-dependent anti-inflammatory effect of new thiourea derivatives of naproxen with selected aromatic amines and esters of aromatic amino acids. The results of the in vivo study indicate that derivatives of m-anisidine (4) and N-methyl tryptophan methyl ester (7) showed the most potent anti-inflammatory activity four hours after injection of carrageenan, with the percentage of inhibition of 54.01% and 54.12%, respectively. In vitro assays of COX-2 inhibition demonstrated that none of the tested compounds achieved 50% inhibition at concentrations lower than 100 µM. On the other hand, the aromatic amine derivatives (1–5) accomplished significant inhibition of 5-LOX, and the lowest IC50 value was observed for compound 4 (0.30 μM). High anti-edematous activity of compound 4 in the rat paw edema model, together with potent inhibition of 5-LOX, highlight this compound as a promising anti-inflammatory agent",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen",
volume = "16",
number = "5",
doi = "10.3390/ph16050666"
}

Nedeljković, N., Dobričić, V., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Jeremić, N., Novaković, J., Jakovljević, V., Vujić, Z.,& Nikolić, M.. (2023). Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals
MDPI., 16(5).
https://doi.org/10.3390/ph16050666

Nedeljković N, Dobričić V, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Jeremić N, Novaković J, Jakovljević V, Vujić Z, Nikolić M. Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals. 2023;16(5).
doi:10.3390/ph16050666 .

Nedeljković, Nikola, Dobričić, Vladimir, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Jeremić, Nevena, Novaković, Jovana, Jakovljević, Vladimir, Vujić, Zorica, Nikolić, Miloš, "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen" in Pharmaceuticals, 16, no. 5 (2023),
https://doi.org/10.3390/ph16050666 . .

TY  - JOUR
AU  - Coskun, Goknil Pelin
AU  - Ozhan, Yagmur
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Reis, Rengin
AU  - Sipahi, Hande
AU  - Sahin, Zafer
AU  - Demirayak, Seref
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4764
AB  - Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.
PB  - MDPI
T2  - Pharmaceutics
T1  - Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer
VL  - 15
IS  - 5
DO  - https://doi.org/10.3390/pharmaceutics15051441
ER  - 

@article{
author = "Coskun, Goknil Pelin and Ozhan, Yagmur and Dobričić, Vladimir and Bošković, Jelena and Reis, Rengin and Sipahi, Hande and Sahin, Zafer and Demirayak, Seref",
year = "2023",
abstract = "Cancer is the disease with the highest mortality. Drug studies contribute to promising treatments; however there is an urgent need for selective drug candidates. Pancreatic cancer is difficult to treat and the cancer progresses rapidly. Unfortunately, current treatments are ineffective. In this study, ten new diarylthiophene-2-carbohydrazide derivatives were synthesized and evaluated for their pharmacological activity. The 2D and 3D anticancer activity studies suggested the compounds 7a, 7d, and 7f were promising. Among these, 7f (4.86 µM) showed the best 2D inhibitory activity against PaCa-2 cells. Compounds 7a, 7d and 7f were also tested for their cytotoxic effects on healthy cell line but only compound 7d showed selectivity. Compounds 7a, 7d, and 7f showed the best 3D cell line inhibitory effect according to spheroid diameters. The compounds were screened for their COX-2 and 5-LOX inhibitory activity. For COX-2, the best IC50 value was observed for 7c (10.13 µM) and all compounds showed significantly lower inhibition compared to standard. In the 5-LOX inhibition study, compounds 7a (3.78 µM), 7c (2.60 µM), 7e (3.3 µM), and 7f (2.94 µM) demonstrated influential activity compared to standard. Regarding molecular docking studies, binding mode of compounds 7c, 7e, and 7f to the 5-LOX enzyme were non-redox or redox types, but not the iron-binding type. As dual inhibitors of 5-LOX and pancreatic cancer cell line, 7a and 7f were identified as the most promising compounds.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer",
volume = "15",
number = "5",
doi = "https://doi.org/10.3390/pharmaceutics15051441"
}

Coskun, G. P., Ozhan, Y., Dobričić, V., Bošković, J., Reis, R., Sipahi, H., Sahin, Z.,& Demirayak, S.. (2023). Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. in Pharmaceutics
MDPI., 15(5).
https://doi.org/https://doi.org/10.3390/pharmaceutics15051441

Coskun GP, Ozhan Y, Dobričić V, Bošković J, Reis R, Sipahi H, Sahin Z, Demirayak S. Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer. in Pharmaceutics. 2023;15(5).
doi:https://doi.org/10.3390/pharmaceutics15051441 .

Coskun, Goknil Pelin, Ozhan, Yagmur, Dobričić, Vladimir, Bošković, Jelena, Reis, Rengin, Sipahi, Hande, Sahin, Zafer, Demirayak, Seref, "Discovery of Novel Thiophene/Hydrazones: In Vitro and In Silico Studies against Pancreatic Cancer" in Pharmaceutics, 15, no. 5 (2023),
https://doi.org/https://doi.org/10.3390/pharmaceutics15051441 . .

TY  - CONF
AU  - Nedeljković, Nikola
AU  - Dobričić, Vladimir
AU  - Bošković, Jelena
AU  - Vesović, Marina
AU  - Bradić, Jovana
AU  - Anđić, Marijana
AU  - Kočović, Aleksandar
AU  - Jeremić, Nevena
AU  - Novaković, Jovana
AU  - Jakovljević, Vladimir
AU  - Vujić, Zorica
AU  - Nikolić, Miloš
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5476
AB  - The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX
inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro
anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing
m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study
was carried out using a carrageenan-induced paw edema model of acute inflammation.
COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using
fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2
software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory
activity to naproxen (56.32%) four hours after injection of carrageenan, with
the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl
tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that
none of the tested compounds achieved 50% inhibition at concentrations below 100 μM,
whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 =
0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested
compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason
why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed
a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl
tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation
in the active site in both cases. The significant in vivo anti-inflammatory activity of
the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this
compound as a promising anti-inflammatory agent.
PB  - Fakultet medicinskih nauka Univerziteta u Kragujevcu
C3  - 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia
T1  - Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5476
ER  - 

@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Bošković, Jelena and Vesović, Marina and Bradić, Jovana and Anđić, Marijana and Kočović, Aleksandar and Jeremić, Nevena and Novaković, Jovana and Jakovljević, Vladimir and Vujić, Zorica and Nikolić, Miloš",
year = "2023",
abstract = "The aim of the conducted study was to develop new potential dual COX-2 and 5-LOX
inhibitors based on naproxen scaffold. We performed the evaluation of in vivo and in vitro
anti-inflammatory activity of newly synthesized thiourea derivatives of naproxen containing
m-anisidine and N-methyl tryptophan methyl ester in a side chain. An in vivo study
was carried out using a carrageenan-induced paw edema model of acute inflammation.
COX-2 and 5-LOX inhibitory potential of synthesized compounds was evaluated using
fluorometric inhibitor screening kits. In silico study was performed in OEDocking 3.2.0.2
software with the FRED tool. Two investigated derivatives exhibited comparable anti-inflammatory
activity to naproxen (56.32%) four hours after injection of carrageenan, with
the percentage of inhibition being 54.01% (m-anisidine derivative) and 54.12% (N-methyl
tryptophan methyl ester derivative). In vitro studies of COX-2 inhibition demonstrated that
none of the tested compounds achieved 50% inhibition at concentrations below 100 μM,
whereas the m-anisidine derivative accomplished comparable inhibition of 5-LOX (IC50 =
0.30 μM) to commercial 5-LOX inhibitor zileuton (IC50 = 0.36 μM). Inability of the tested
compounds to form three hydrogen bonds with ARG120 and TYR355 could be a reason
why these compounds showed weak COX-2 inhibition. The m-anisidine derivative formed
a more stable complex with the 5-LOX enzyme (−8.39 kcal/mol), compared to N-methyl
tryptophan methyl ester derivative (−7.98 kcal/mol), with the absence of the iron ion chelation
in the active site in both cases. The significant in vivo anti-inflammatory activity of
the m-anisidine derivative, together with the potent inhibition of 5-LOX, highlighted this
compound as a promising anti-inflammatory agent.",
publisher = "Fakultet medicinskih nauka Univerziteta u Kragujevcu",
journal = "9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia",
title = "Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5476"
}

Nedeljković, N., Dobričić, V., Bošković, J., Vesović, M., Bradić, J., Anđić, M., Kočović, A., Jeremić, N., Novaković, J., Jakovljević, V., Vujić, Z.,& Nikolić, M.. (2023). Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach. in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia
Fakultet medicinskih nauka Univerziteta u Kragujevcu..
https://hdl.handle.net/21.15107/rcub_farfar_5476

Nedeljković N, Dobričić V, Bošković J, Vesović M, Bradić J, Anđić M, Kočović A, Jeremić N, Novaković J, Jakovljević V, Vujić Z, Nikolić M. Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach. in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia. 2023;.
https://hdl.handle.net/21.15107/rcub_farfar_5476 .

Nedeljković, Nikola, Dobričić, Vladimir, Bošković, Jelena, Vesović, Marina, Bradić, Jovana, Anđić, Marijana, Kočović, Aleksandar, Jeremić, Nevena, Novaković, Jovana, Jakovljević, Vladimir, Vujić, Zorica, Nikolić, Miloš, "Selected thiourea derivatives of naproxen as potential anti-inflammatory agents: in vivo, in vitro, and in silico approach" in 9th International Congress of Pathophysiology and 5th Congress of Physiological Sciences of Serbia with International Participation, July 4th - 6th, 2023. Belgrade, Serbia (2023),
https://hdl.handle.net/21.15107/rcub_farfar_5476 .

TY  - CONF
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Nedeljković, Nikola
AU  - Nikolić, Miloš
AU  - Vujić, Zorica
AU  - Čudina, Olivera
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5458
AB  - The pathogenesis and progression of a various diseases, such as cancer, rheumatoid arthritis, autoimmune, cardiovascular and neurodegenerative diseases, are closely related to chronic inflammatory processes. ...
PB  - European Federation for Medicinal chemistry and Chemical biology (EFMC)
C3  - EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts
T1  - Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors
SP  - 154
EP  - 154
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5458
ER  - 

@conference{
author = "Bošković, Jelena and Dobričić, Vladimir and Nedeljković, Nikola and Nikolić, Miloš and Vujić, Zorica and Čudina, Olivera",
year = "2023",
abstract = "The pathogenesis and progression of a various diseases, such as cancer, rheumatoid arthritis, autoimmune, cardiovascular and neurodegenerative diseases, are closely related to chronic inflammatory processes. ...",
publisher = "European Federation for Medicinal chemistry and Chemical biology (EFMC)",
journal = "EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts",
title = "Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors",
pages = "154-154",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5458"
}

Bošković, J., Dobričić, V., Nedeljković, N., Nikolić, M., Vujić, Z.,& Čudina, O.. (2023). Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors. in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts
European Federation for Medicinal chemistry and Chemical biology (EFMC)., 154-154.
https://hdl.handle.net/21.15107/rcub_farfar_5458

Bošković J, Dobričić V, Nedeljković N, Nikolić M, Vujić Z, Čudina O. Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors. in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts. 2023;:154-154.
https://hdl.handle.net/21.15107/rcub_farfar_5458 .

Bošković, Jelena, Dobričić, Vladimir, Nedeljković, Nikola, Nikolić, Miloš, Vujić, Zorica, Čudina, Olivera, "Synthesis and investigation of enzyme inhibition of potential dual COX-2 and 5-LOX inhibitors" in EFMC-ASMC, IX EFMC Internatinal Symposium on Advances in Synthetic and Medicinal Chemistry, September 3 - 7. 2023, Zagreb, Croatia , Book of Abstracts (2023):154-154,
https://hdl.handle.net/21.15107/rcub_farfar_5458 .

TY  - JOUR
AU  - Savić, Jelena
AU  - Antonijević, Marija
AU  - Crevar, Milkica
AU  - Brborić, Jasmina
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4978
AB  - Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and
diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors
target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer,
atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and
hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of
selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based
on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids,
two groups of compounds were designed: analogs in which one of the benzene rings was replaced
by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic
acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the
enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were
compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding
energies than the designed acids, which makes them attractive target compounds for synthesis
and further examination.
AB  - Neselektivni nesteroidni antiinflamatorni lekovi poput aspirina, ibuprofena i diklofenaka
inhibiraju enzime ciklooksigenazu-1 i ciklooksigenazu-2, a selektivni inhibitori ciljaju
ciklooksigenazu-2 koja je prekomerno izražena u inflamaciji, ali takođe i kod kancera,
ateroskleroze, Parkinsonove i Alchajmerove bolesti. Potencijalni kardiovaskularni i hepatički
neželjeni efekti selektivnih inhibitora ciklooksigenaze-2 su ograničili njihovu primenu. Razvoj
selektivnih i bezbednih inhibitora ciklooksigenaze-2 ostaje veoma prioritetna oblast u otkrivanju
lekova. Na osnovu strukture prethodno istraživanih novosintetisanih β-hidroksi-β-arilpropanskih
kiselina dizajnirane su dve grupe jedinjenja: analozi u kojima je jedan od benzenovih prstenova
zamenjen pirazolom, uz zadržavanje karboksilne grupe, i amidi β-hidroksi-β-arilpropanskih
kiselina sa pirazolom. Program AutoDock Vina 1.2.0 je korišćen za dokovanje dizajniranih
jedinjenja u 3D strukturu katalitičkog mesta enzima ciklooksigenaze-2, a ostvarene interakcije su
upoređene sa interakcijama koje ostvaruje selektivni inhibitor celekoksib. Amidi su imali nižu
energiju vezivanja od kiselina, što ih čini dobrim kandidatima za sintezu.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
T2  - Arhiv za farmaciju
T1  - Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site
T1  - Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2
VL  - 73
IS  - 3
SP  - 205
EP  - 215
DO  - 10.5937/arhfarm73-44720
ER  - 

@article{
author = "Savić, Jelena and Antonijević, Marija and Crevar, Milkica and Brborić, Jasmina",
year = "2023",
abstract = "Whereas nonselective nonsteroidal anti-inflammatory drugs, such as aspirin, ibuprofen and
diclofenac, inhibit both cyclooxygenase-1 and cyclooxigenase-2 enzymes, selective inhibitors
target cyclooxygenase-2, which is overexpressed in inflammation, but also in cancer,
atherosclerosis, Alzheimer's disease, and Parkinson`s disease. Potential cardiovascular and
hepatic side effects of cyclooxygenase-2 inhibitors have limited their use. The development of
selective and safe cyclooxygenase-2 inhibitors remains a high priority in drug discovery. Based
on the structure of previously investigated newly synthesized β-hydroxy-β-arylpropanoic acids,
two groups of compounds were designed: analogs in which one of the benzene rings was replaced
by a pyrazole, while the carboxyl group was retained, and amides of β-hydroxy-β-arylpropanoic
acids with pyrazole. The compounds were docked into the 3D structure of the catalytic site of the
enzyme cyclooxygenase-2 using AutoDock Vina 1.2.0. and the obtained interactions were
compared with the interactions of celecoxib, a selective inhibitor. The amides had lower binding
energies than the designed acids, which makes them attractive target compounds for synthesis
and further examination., Neselektivni nesteroidni antiinflamatorni lekovi poput aspirina, ibuprofena i diklofenaka
inhibiraju enzime ciklooksigenazu-1 i ciklooksigenazu-2, a selektivni inhibitori ciljaju
ciklooksigenazu-2 koja je prekomerno izražena u inflamaciji, ali takođe i kod kancera,
ateroskleroze, Parkinsonove i Alchajmerove bolesti. Potencijalni kardiovaskularni i hepatički
neželjeni efekti selektivnih inhibitora ciklooksigenaze-2 su ograničili njihovu primenu. Razvoj
selektivnih i bezbednih inhibitora ciklooksigenaze-2 ostaje veoma prioritetna oblast u otkrivanju
lekova. Na osnovu strukture prethodno istraživanih novosintetisanih β-hidroksi-β-arilpropanskih
kiselina dizajnirane su dve grupe jedinjenja: analozi u kojima je jedan od benzenovih prstenova
zamenjen pirazolom, uz zadržavanje karboksilne grupe, i amidi β-hidroksi-β-arilpropanskih
kiselina sa pirazolom. Program AutoDock Vina 1.2.0 je korišćen za dokovanje dizajniranih
jedinjenja u 3D strukturu katalitičkog mesta enzima ciklooksigenaze-2, a ostvarene interakcije su
upoređene sa interakcijama koje ostvaruje selektivni inhibitor celekoksib. Amidi su imali nižu
energiju vezivanja od kiselina, što ih čini dobrim kandidatima za sintezu.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site, Doking studije nekih jedinjenja sa pirazolom u aktivnom mestu ciklooksigenaze-2",
volume = "73",
number = "3",
pages = "205-215",
doi = "10.5937/arhfarm73-44720"
}

Savić, J., Antonijević, M., Crevar, M.,& Brborić, J.. (2023). Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 73(3), 205-215.
https://doi.org/10.5937/arhfarm73-44720

Savić J, Antonijević M, Crevar M, Brborić J. Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site. in Arhiv za farmaciju. 2023;73(3):205-215.
doi:10.5937/arhfarm73-44720 .

Savić, Jelena, Antonijević, Marija, Crevar, Milkica, Brborić, Jasmina, "Docking studies of some pyrazole containing compounds in the cyclooxygenase-2 active site" in Arhiv za farmaciju, 73, no. 3 (2023):205-215,
https://doi.org/10.5937/arhfarm73-44720 . .

TY  - JOUR
AU  - Bošković, Jelena
AU  - Dobričić, Vladimir
AU  - Mihajlović, Marija
AU  - Kotur-Stevuljević, Jelena
AU  - Čudina, Olivera
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4755
AB  - Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests.
The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.
PB  - MDPI
T2  - Pharmaceuticals
T1  - Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors
VL  - 16
IS  - 4
DO  - https://doi.org/10.3390/ph16040549
ER  - 

@article{
author = "Bošković, Jelena and Dobričić, Vladimir and Mihajlović, Marija and Kotur-Stevuljević, Jelena and Čudina, Olivera",
year = "2023",
abstract = "Various dual inhibitors of COX-2 and 5-LOX enzymes have been developed so far in order to obtain more effective and safer anti-inflammatory drugs. The aim of this study was to design and synthesize new dual COX-2 and 5-LOX inhibitors, and to evaluate their enzyme inhibition potential and redox properties. Thirteen compounds (1–13) were designed taking into account structural requirements for dual COX-2 and 5-LOX inhibition and antioxidant activity, synthesized, and structurally characterized. These compounds can be classified as N-hydroxyurea derivatives (1, 2 and 3), 3,5-di-tert-butylphenol derivatives (4, 5, 6, 7 and 13), urea derivatives (8, 9 and 10) and “type B hydroxamic acids” (11 and 12). COX-1, COX-2 and 5-LOX inhibitory activities were evaluated using fluorometric inhibitor screening kits. The evaluation of the redox activity of newly synthesized compounds was performed in vitro in the human serum pool using redox status tests.
The prooxidative score, the antioxidative score and the oxy-score were calculated. Seven out of thirteen synthesized compounds (1, 2, 3, 5, 6, 11 and 12) proved to be dual COX-2 and 5-LOX inhibitors. These compounds expressed good COX-2/COX-1 selectivity. Moreover, dual inhibitors 1, 3, 5, 11 and 12 showed good antioxidant properties.",
publisher = "MDPI",
journal = "Pharmaceuticals",
title = "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors",
volume = "16",
number = "4",
doi = "https://doi.org/10.3390/ph16040549"
}

Bošković, J., Dobričić, V., Mihajlović, M., Kotur-Stevuljević, J.,& Čudina, O.. (2023). Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. in Pharmaceuticals
MDPI., 16(4).
https://doi.org/https://doi.org/10.3390/ph16040549

Bošković J, Dobričić V, Mihajlović M, Kotur-Stevuljević J, Čudina O. Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors. in Pharmaceuticals. 2023;16(4).
doi:https://doi.org/10.3390/ph16040549 .

Bošković, Jelena, Dobričić, Vladimir, Mihajlović, Marija, Kotur-Stevuljević, Jelena, Čudina, Olivera, "Synthesis, Evaluation of Enzyme Inhibition and Redox Properties of Potential Dual COX-2 and 5-LOX Inhibitors" in Pharmaceuticals, 16, no. 4 (2023),
https://doi.org/https://doi.org/10.3390/ph16040549 . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Keta, Otilija
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4489
AB  - It is estimated that up to 20% of cancer-related deaths are linked with inflammation
(1). Inhibition of inflammatory enzymes COX-2 and 5-LOX impacts cancer cells directly, or
indirectly via tumor microenvironment. Wider anticancer potential has been investigated for
a small group of COX-2 inhibitors (2), while there are no such data for dual COX-2 and 5-LOX
inhibitors. The main aim of the project is to select the most promising anticancer drug
candidates from a group of COX-2 and dual COX-2 and 5-LOX inhibitors (newly synthesized
and previously synthesized). New compounds will be designed using structure-based and
ligand-based in silico methods and synthesized. Cytotoxicity will be evaluated towards four
cancer cell lines by MTT assay. Wider anticancer potential of selected compounds, which
includes synergism with conventional chemotherapy and radiotherapy, inhibition of
angiogenesis and activity towards multidrug resistant cancer cells, will be investigated and
lead compounds will be identified. Mechanisms of action of lead compounds will be
proposed after bioinformatics analysis of genes expression. In vitro evaluation of passive
gastrointestinal absorption (PAMPA and BMC), binding to human serum albumin (HPLC and
electrochemistry) and metabolism (human liver microsomes) will be performed. QSPR,
QSRR and QSMARt models will be created and, together with analysis of metabolism, will be
used for the optimization of structures of lead compounds. The project will result in the
development of new anticancer drug candidates, make new and strengthen previously
established scientific collaborations and give starting point for potential clinical evaluations
of lead compounds.
AB  - Procenjuje se da je do 20% smrtnih slučajeva koji su posledica tumora povezano sa
inflamacijom (1). Inhibicija enzima inflamacije COX-2 i 5-LOX utiče na tumorske ćelije
direktno ili indirektno preko tumorskog mikrookruženja. Širi antitumorski potencijal je do
sada ispitan za malu grupu COX-2 inhibitora (2), dok takva istraživanja nisu do sada vršena
na dualnim COX-2 i 5-LOX inhibitorima. Glavni cilj projekta je da se identifikuju najbolji
kandidati za antitumorske lekove iz grupe COX-2 i grupe dualnih inhibitora COX-2 i 5-LOX
(novosintetisana i prethodno sintetisana jedinjenja). Nova jedinjenja će biti dizajnirana
primenom in silico metoda koje se zasnivaju na poznavanju strukture receptora i liganda,
nakon čega će biti sintetisana. Citotoksičnost će biti ispitana na četiri tumorske ćelijske linije
primenom MTT testa. Širi antitumorski potencijal odabranih jedinjenja, koji podrazumeva
sinergističko dejstvo sa konvencionalnom hemoterapijom i radioterapijom, inhibiciju
angiogeneze i aktivnost prema multidrug rezistentnim ćelijskim linijama, će biti ispitan,
nakon čega će biti identifikovana vodeća (lead) jedinjenja. Mehanizam delovanja vodećih
jedinjenja će biti predložen nakon bioinformatičke analize ekspresije gena. Biće izvršena in
vitro procena pasivne gastrointestinalne apsorpcije (PAMPA i BMC metodama), vezivanja za
humani serumski albumin (HPLC i elektrohemijkim metodama) i metabolizma primenom
humanih mikrozomnih enzima jetre. QSPR, QSRR i QSMARt modeli će biti formirani i, zajedno
sa analizom metabolizma, biće upotrebljeni za optimizaciju struktura vodećih jedinjenja.
Rezultat projekta će biti novi kandidati za antitumorske lekove, uspostavljanje novih i
jačanje postojećih naučno-istraživačkih saradnji i postavljanje polazne tačke za potencijalna
klinička ispitivanja vodećih jedinjenja.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity
T1  - Primena veze između inflamacije i tumora u razvoju jedinjenja sa antitumorskom aktivnošću
VL  - 72
IS  - 4 suplement
SP  - S178
EP  - S179
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4489
ER  - 

@conference{
author = "Dobričić, Vladimir and Keta, Otilija",
year = "2022",
abstract = "It is estimated that up to 20% of cancer-related deaths are linked with inflammation
(1). Inhibition of inflammatory enzymes COX-2 and 5-LOX impacts cancer cells directly, or
indirectly via tumor microenvironment. Wider anticancer potential has been investigated for
a small group of COX-2 inhibitors (2), while there are no such data for dual COX-2 and 5-LOX
inhibitors. The main aim of the project is to select the most promising anticancer drug
candidates from a group of COX-2 and dual COX-2 and 5-LOX inhibitors (newly synthesized
and previously synthesized). New compounds will be designed using structure-based and
ligand-based in silico methods and synthesized. Cytotoxicity will be evaluated towards four
cancer cell lines by MTT assay. Wider anticancer potential of selected compounds, which
includes synergism with conventional chemotherapy and radiotherapy, inhibition of
angiogenesis and activity towards multidrug resistant cancer cells, will be investigated and
lead compounds will be identified. Mechanisms of action of lead compounds will be
proposed after bioinformatics analysis of genes expression. In vitro evaluation of passive
gastrointestinal absorption (PAMPA and BMC), binding to human serum albumin (HPLC and
electrochemistry) and metabolism (human liver microsomes) will be performed. QSPR,
QSRR and QSMARt models will be created and, together with analysis of metabolism, will be
used for the optimization of structures of lead compounds. The project will result in the
development of new anticancer drug candidates, make new and strengthen previously
established scientific collaborations and give starting point for potential clinical evaluations
of lead compounds., Procenjuje se da je do 20% smrtnih slučajeva koji su posledica tumora povezano sa
inflamacijom (1). Inhibicija enzima inflamacije COX-2 i 5-LOX utiče na tumorske ćelije
direktno ili indirektno preko tumorskog mikrookruženja. Širi antitumorski potencijal je do
sada ispitan za malu grupu COX-2 inhibitora (2), dok takva istraživanja nisu do sada vršena
na dualnim COX-2 i 5-LOX inhibitorima. Glavni cilj projekta je da se identifikuju najbolji
kandidati za antitumorske lekove iz grupe COX-2 i grupe dualnih inhibitora COX-2 i 5-LOX
(novosintetisana i prethodno sintetisana jedinjenja). Nova jedinjenja će biti dizajnirana
primenom in silico metoda koje se zasnivaju na poznavanju strukture receptora i liganda,
nakon čega će biti sintetisana. Citotoksičnost će biti ispitana na četiri tumorske ćelijske linije
primenom MTT testa. Širi antitumorski potencijal odabranih jedinjenja, koji podrazumeva
sinergističko dejstvo sa konvencionalnom hemoterapijom i radioterapijom, inhibiciju
angiogeneze i aktivnost prema multidrug rezistentnim ćelijskim linijama, će biti ispitan,
nakon čega će biti identifikovana vodeća (lead) jedinjenja. Mehanizam delovanja vodećih
jedinjenja će biti predložen nakon bioinformatičke analize ekspresije gena. Biće izvršena in
vitro procena pasivne gastrointestinalne apsorpcije (PAMPA i BMC metodama), vezivanja za
humani serumski albumin (HPLC i elektrohemijkim metodama) i metabolizma primenom
humanih mikrozomnih enzima jetre. QSPR, QSRR i QSMARt modeli će biti formirani i, zajedno
sa analizom metabolizma, biće upotrebljeni za optimizaciju struktura vodećih jedinjenja.
Rezultat projekta će biti novi kandidati za antitumorske lekove, uspostavljanje novih i
jačanje postojećih naučno-istraživačkih saradnji i postavljanje polazne tačke za potencijalna
klinička ispitivanja vodećih jedinjenja.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity, Primena veze između inflamacije i tumora u razvoju jedinjenja sa antitumorskom aktivnošću",
volume = "72",
number = "4 suplement",
pages = "S178-S179",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4489"
}

Dobričić, V.,& Keta, O.. (2022). Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S178-S179.
https://hdl.handle.net/21.15107/rcub_farfar_4489

Dobričić V, Keta O. Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity. in Arhiv za farmaciju. 2022;72(4 suplement):S178-S179.
https://hdl.handle.net/21.15107/rcub_farfar_4489 .

Dobričić, Vladimir, Keta, Otilija, "Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S178-S179,
https://hdl.handle.net/21.15107/rcub_farfar_4489 .

TY  - CONF
AU  - Savić, Jelena
AU  - Brborić, Jasmina
PY  - 2022
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4445
AB  - Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for nearly a century
for alleviation of symptoms of acute and chronic inflammation and represent one of the most
used groups of drugs in the general population. NSAIDs group is very numerous and it
includes different chemical structures. The main mechanism of action of these drugs is the
inhibition of enzyme cyclooxygenase (COX) which catalyzes prostaglandin production (of
which some are inflammatory mediators) from arachidonic acid and depending on whether
they inhibit both isoforms (COX-1 and COX-2) and just COX-2 they can be classified as
nonselective and selective. The need for finding the new NSAIDs with fewer side effects is
still persistent because nonselective NSAIDs often cause gastrointestinal side effects which
vary from mild to very serious like bleeding, while some selective are withdrawn because of
serious cardiovascular side effects with death outcome (1). Several epidemiologic studies
have shown a negative correlation between NSAID use and the occurrence of Alzheimer`s
disease, as well as some types of cancer, particularly colorectal and breast cancer. The
development of compounds that would be used in Alzheimer`s disease therapy is direct on
structures that exhibit more effects at the same time, one of which is anti-inflammatory
effect mediated via COX-2 inhibition. Although chemoprevention mechanisms are not
completely delineated, it is indisputable that both COX isoforms play a role in carcinogenesis,
and these findings opened a new field of research for the design and synthesis of new COX
inhibitors with chemoprotective, antiangiogenic, and cytotoxic activity.
AB  - Nesteroidni antiinflamatorni lekovi (NSAIL) se koriste za ublažavanje simptoma
akutne i hronične inflamacije već skoro čitav vek i predstavljaju jednu od najčešće
primenjivanih grupa lekova u najširoj populaciji. Grupa NSAIL je veoma brojna i obuhvata
različite hemijske strukture. Glavni mehanizam delovanja ovih lekova je inhibicija enzima
ciklooksigenaze (COX) koji katalizuje produkciju prostaglandina (od kojih su neki medijatori
inflamacije) iz arahidonske kiseline, a u zavisnosti od toga da li inhibiraju obe izoforme
(COX-1 i COX-2) ili samo COX-2, dele se na neselektivne i selektivne. Potreba za otkrivanjem
novih NSAIL sa manje neželjenih efekata je i danas aktuelna, jer neselektivni NSAIL često
izazivaju neželjene gastrointestinalne efekte koji variraju od blagih do veoma ozbiljnih kao
što je krvarenje, a neki selektivni lekovi su povučeni iz upotrebe zbog ozbiljnih neželjenih
kardiovaskularnih efekata sa smrtnim ishodom (1). Nekoliko epidemioloških studija je
pokazalo da postoji negativna korelacija između upotrebe NSAIL i pojave Alchajmerove
bolesti, kao i nekih tipova kancera, a naročito kolorektalnog i kancera dojke. Razvoj
jedinjenja koja bi se koristila u terapiji Alchajmerove bolesti je usmeren na strukture koje
istovremeno imaju više efekata, a jedan od njih je antiinflamatorni posredovan inhibicijom
COX-2. Iako mehanizmi hemoprevencije nisu potpuno rasvetljeni, nesporno je da postoji
uloga obe COX izoforme u karcinogenezi, a ova saznanja su otvorila novo polje istraživanja ka
dizajniranju i sintezi novih COX inhibitora sa hemoprotektivnom, antiangiogeneznom i
citotoksičnom aktivnošću.
PB  - Savez farmaceutskih udruženja Srbije (SFUS)
C3  - Arhiv za farmaciju
T1  - New directions in the development of cyclooxygenase inhibitors
T1  - Novi pravci u razvoju inhibitora ciklooksigenaze
VL  - 72
IS  - 4 suplement
SP  - S53
EP  - S54
UR  - https://hdl.handle.net/21.15107/rcub_farfar_4445
ER  - 

@conference{
author = "Savić, Jelena and Brborić, Jasmina",
year = "2022",
abstract = "Nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for nearly a century
for alleviation of symptoms of acute and chronic inflammation and represent one of the most
used groups of drugs in the general population. NSAIDs group is very numerous and it
includes different chemical structures. The main mechanism of action of these drugs is the
inhibition of enzyme cyclooxygenase (COX) which catalyzes prostaglandin production (of
which some are inflammatory mediators) from arachidonic acid and depending on whether
they inhibit both isoforms (COX-1 and COX-2) and just COX-2 they can be classified as
nonselective and selective. The need for finding the new NSAIDs with fewer side effects is
still persistent because nonselective NSAIDs often cause gastrointestinal side effects which
vary from mild to very serious like bleeding, while some selective are withdrawn because of
serious cardiovascular side effects with death outcome (1). Several epidemiologic studies
have shown a negative correlation between NSAID use and the occurrence of Alzheimer`s
disease, as well as some types of cancer, particularly colorectal and breast cancer. The
development of compounds that would be used in Alzheimer`s disease therapy is direct on
structures that exhibit more effects at the same time, one of which is anti-inflammatory
effect mediated via COX-2 inhibition. Although chemoprevention mechanisms are not
completely delineated, it is indisputable that both COX isoforms play a role in carcinogenesis,
and these findings opened a new field of research for the design and synthesis of new COX
inhibitors with chemoprotective, antiangiogenic, and cytotoxic activity., Nesteroidni antiinflamatorni lekovi (NSAIL) se koriste za ublažavanje simptoma
akutne i hronične inflamacije već skoro čitav vek i predstavljaju jednu od najčešće
primenjivanih grupa lekova u najširoj populaciji. Grupa NSAIL je veoma brojna i obuhvata
različite hemijske strukture. Glavni mehanizam delovanja ovih lekova je inhibicija enzima
ciklooksigenaze (COX) koji katalizuje produkciju prostaglandina (od kojih su neki medijatori
inflamacije) iz arahidonske kiseline, a u zavisnosti od toga da li inhibiraju obe izoforme
(COX-1 i COX-2) ili samo COX-2, dele se na neselektivne i selektivne. Potreba za otkrivanjem
novih NSAIL sa manje neželjenih efekata je i danas aktuelna, jer neselektivni NSAIL često
izazivaju neželjene gastrointestinalne efekte koji variraju od blagih do veoma ozbiljnih kao
što je krvarenje, a neki selektivni lekovi su povučeni iz upotrebe zbog ozbiljnih neželjenih
kardiovaskularnih efekata sa smrtnim ishodom (1). Nekoliko epidemioloških studija je
pokazalo da postoji negativna korelacija između upotrebe NSAIL i pojave Alchajmerove
bolesti, kao i nekih tipova kancera, a naročito kolorektalnog i kancera dojke. Razvoj
jedinjenja koja bi se koristila u terapiji Alchajmerove bolesti je usmeren na strukture koje
istovremeno imaju više efekata, a jedan od njih je antiinflamatorni posredovan inhibicijom
COX-2. Iako mehanizmi hemoprevencije nisu potpuno rasvetljeni, nesporno je da postoji
uloga obe COX izoforme u karcinogenezi, a ova saznanja su otvorila novo polje istraživanja ka
dizajniranju i sintezi novih COX inhibitora sa hemoprotektivnom, antiangiogeneznom i
citotoksičnom aktivnošću.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "New directions in the development of cyclooxygenase inhibitors, Novi pravci u razvoju inhibitora ciklooksigenaze",
volume = "72",
number = "4 suplement",
pages = "S53-S54",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4445"
}

Savić, J.,& Brborić, J.. (2022). New directions in the development of cyclooxygenase inhibitors. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije (SFUS)., 72(4 suplement), S53-S54.
https://hdl.handle.net/21.15107/rcub_farfar_4445

Savić J, Brborić J. New directions in the development of cyclooxygenase inhibitors. in Arhiv za farmaciju. 2022;72(4 suplement):S53-S54.
https://hdl.handle.net/21.15107/rcub_farfar_4445 .

Savić, Jelena, Brborić, Jasmina, "New directions in the development of cyclooxygenase inhibitors" in Arhiv za farmaciju, 72, no. 4 suplement (2022):S53-S54,
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