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Design and synthesis of new 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety as selective COX-2 inhibitors

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Abstract

A new series of 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety, COX-2 pharmacophore, was designed and synthesized. The synthetic pathway for preparation of the new 1,2,3-triazole derivatives started with the preparation of the two key intermediates: 4-(4-acetyl-5-methyl-1H-1,2,3-triazol-1-yl)benzenesulfonamide 3 and 4-(4-(hydrazinecarbonyl)-5-methyl-1H-1,2,3-triazol-1-yl)benzenesulfonamide 13 that were then used to synthesize the new triheterocycles. All the synthesized compounds were virtually screened for their binding interactions with both COX isozymes. Compounds showing similar conformation to that of celecoxib, the co-crystallized ligand, and exhibited reasonable interactions, were then evaluated for their in vitro COX-1 and COX-2 inhibition activity. All the compounds under investigation were found to be active as COX-1 and COX-2 inhibitors. Compounds 11 and 13 showed the highest activity as COX-2 inhibitors with IC50 values of 2.618 and 2.92 µM, respectively. On the other hand, compound 13 showed moderate selectivity toward COX-2 inhibition with selectivity ratio of 6.99. Summing up, as confirmed by in vitro and in silico results, the triazolyl benzenesulfonamide derivative 13-bearing unsubstituted hydrazide moiety can be considered as suitable candidate for further investigation as selective COX-2 inhibitor.

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Authors and Affiliations

  1. Chemical Industries Research Division, National Research Centre, Giza, Egypt

    Mohamed S. Bekheit

  2. Applied Organic Chemistry Departmet, National Research Centre, Giza, Egypt

    Hanan A. Mohamed & Bakr F. Abdel-Wahab

  3. Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Marwa A. Fouad

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Bekheit, M.S., Mohamed, H.A., Abdel-Wahab, B.F. et al. Design and synthesis of new 1,4,5-trisubstituted triazole-bearing benzenesulphonamide moiety as selective COX-2 inhibitors. Med Chem Res 30, 1125–1138 (2021). https://doi.org/10.1007/s00044-021-02716-7

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