Pharmaceuticals (Apr 2023)

Synthesis and Investigation of Anti-Inflammatory Activity of New Thiourea Derivatives of Naproxen

  • Nikola Nedeljković,
  • Vladimir Dobričić,
  • Jelena Bošković,
  • Marina Vesović,
  • Jovana Bradić,
  • Marijana Anđić,
  • Aleksandar Kočović,
  • Nevena Jeremić,
  • Jovana Novaković,
  • Vladimir Jakovljević,
  • Zorica Vujić,
  • Miloš Nikolić

DOI
https://doi.org/10.3390/ph16050666
Journal volume & issue
Vol. 16, no. 5
p. 666

Abstract

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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.

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