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  - 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 .