Novel 1-[4-(Aminosulfonyl)phenyl]-1H-1,2,4-triazole derivatives with remarkable selective COX-2 inhibition: Design, synthesis, molecular docking, anti-inflammatory and ulcerogenicity studies

•A series of novel 1,2,4-triazole derivatives were synthesized.•Most of the tested compounds exhibited remarkable anti-inflammatory activity.•Most of the newly developed compounds showed excellent selectivity towards human COX-2.•Docking studies results revealed that compounds 6h and 6j showed lower CDOCKER energies.

A novel series of 1,2,4-triazole derivatives were synthesized and confirmed with different spectroscopic techniques. The prepared compounds exhibited remarkable anti-inflammatory activity comparable to that of indomethacin and celecoxib after 3 h. The tested compounds exhibited very low incidence of gastric ulceration compared to indomethacin. Most of the newly developed compounds showed excellent selectivity towards human COX-2 with selectivity indices (COX-1 IC50/COX-2 IC50) ranged from 62.5 to 2127. Docking studies results revealed that the highly selective tested compounds 6h and 6j showed lower CDOCKER energies, which means that they require less energy for proper interaction with the enzyme. The additional H-bonds with the oxygen of the amide and/or H of NH of the amide with the amino acid residues may be responsible for the higher binding affinity of this group of compounds towards COX-2.

Graphical abstractNovel 1,2,4-triazole derivatives as new strategy for anti-inflammatory activity and selective COX-2 inhibition.Figure optionsDownload full-size imageDownload as PowerPoint slide