Urease inhibitory activity on 1,2,3-triazoles-linked indomethacin derivatives; in vitro and in silico studies

The current research is based on the biology-oriented drug synthesis (BIODS) approach for synthesizing 1,2,3-triazoles-linked indomethacin derivatives ( 5-20 ). The multi-step synthesis from indomethacin ( 1 ) under base-catalyzed conditions afforded propargyl ester ( 2 ), which was further reacted with substituted azides ( 4a-p ) of acetophenone ( 3a-p ) to afford corresponding 1,2,3-triazole derivatives ( 5-20 ) in excellent yields. Structures of all synthetic derivatives were elucidated through various spectroscopic techniques such as UV, IR, EI-MS, HR-MS, 1 H NMR, 13 C NMR, and 2D-NMR. All compounds 5-20 were evaluated for their inhibitory potential against the urease enzyme, which showed good inhibition in the range of IC50 = 21.7 +/- 0.28 -89.5 +/- 0.34 mu M compared to the standard thiourea (IC50 = 22.4 +/- 0.29 mu M). Com-pounds 5 (IC50 = 22.8 +/- 0.78 mu M), 10 (IC50 = 22.8 +/- 0.78 mu M), and 18 (IC50 = 21.7 +/- 0.28 mu M) were found to be most active and could serve as an attractive building block in the search for novel urease in-hibitors. To ensure the accuracy of these interpretations, in silico analysis was also carried out. The results showed a strong correlation between the bioactivities and the docking investigations.(c) 2023 Elsevier B.V. All rights reserved.

Automated summary

The current research focuses on synthesizing 1,2,3-triazole-linked indomethacin derivatives and evaluating their inhibitory potential against the urease enzyme. Compounds 5, 10, and 18 showed the highest activity and could be used as building blocks for novel urease inhibitors. The structures of the synthetic derivatives were confirmed through various spectroscopic techniques and validated through in silico analysis.