Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen
Authors
Nedeljković, NikolaDobričić, Vladimir

Bošković, Jelena

Vesović, Marina
Bradić, Jovana
Anđić, Marijana
Kočović, Aleksandar
Jeremić, Nevena
Novaković, Jovana
Jakovljević, Vladimir
Vujić, Zorica

Nikolić, Miloš

Article (Published version)
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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
Keywords:
naproxen; thiourea; carrageenan; paw edema; anti-inflammatory activity; COX-2; 5-LOX; molecular docking; FREDSource:
Pharmaceuticals, 2023, 16, 5, 666-Funding / projects:
- Science Fund of the Republic of Serbia, 7739840, Utilization of interplay between inflammation and cancer in the development of compounds with anticancer activity— INFCANPLAY
- Ministry of Science, Technological Development and Innovation, Republic of Serbia through Grant Agreements with University of Belgrade—Faculty of Pharmacy No: 451-03-47/2023-01/200161
- Ministry of Science, Technological Development and Innovation, Republic of Serbia through Grant Agreements with University of Kragujevac—Faculty of Medical Sciences No: 451-03-47/2023-01/200111
- Faculty of Medical Sciences, University of Kragujevac (Junior Project 11/20)
Note:
- Molim da se ovaj rad mapira u podkolekciju "InfCanPlay", kao deo projekta IDEJE čiji je rukovodilac dr Vladimir Dobričić, vanr. prof.
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PharmacyTY - 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 T2 - Pharmaceuticals T1 - Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen VL - 16 IS - 5 SP - 666 DO - https://doi.org/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", journal = "Pharmaceuticals", title = "Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen", volume = "16", number = "5", pages = "666", doi = "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.. (2023). Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen. in Pharmaceuticals, 16(5), 666. https://doi.org/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):666. doi:https://doi.org/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):666, https://doi.org/https://doi.org/10.3390/ ph16050666 . .