Abstract
•Synthesis of a library of 1,2,3-triazoles-linked indomethacin derivatives 5–20.•Structural characterization by spectroscopic techniques.•Compounds were identified as good to moderate inhibitors of urease enzyme.•Structure-activity relationship (SAR).•Assessment of binding interactions of ligands with the active pocket of enzymes.
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, 1H NMR, 13C 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 μM compared to the standard thiourea (IC50 = 22.4 ± 0.29 μM). Compounds 5 (IC50 = 22.8 ± 0.78 μM), 10 (IC50 = 22.8 ± 0.78 μM), and 18 (IC50 = 21.7 ± 0.28 μM) were found to be most active and could serve as an attractive building block in the search for novel urease inhibitors. 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.
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