Synthesis, antimicrobial and α-glucosidase inhibition of new benzimidazole-1,2,3-triazole-indoline derivatives: a combined experimental and computational venture

Abstract

In the current research work, a new series of benzimidazole-1,2,3-triazole-indoline derivatives (5a–r) were designed and synthesized by employing click reaction between substituted N-propargylated benzimidazole derivatives and in situ formed substituted 2-azido-1-(indolin-1-yl)ethanone derivatives in moderate to good yields. The structure of the prepared compounds was confirmed with the help of 1D, 2D-NMR, FTIR and HRMS. The synthesized compounds have been evaluated for their biocidal effects against four bacterial and two fungal strains. The obtained results indicate stronger inhibitory effect of compound 5o against E. coli, while compound 5r showed good inhibition against all the tested strains except B. subtilis. In vitro α-glucosidase inhibition of all synthesized derivatives identified 5p (IC50 value = 0.015 ± 0.0003 μmol/mL) and 5r (IC50 value = 0.018 ± 0.0008 μmol/mL) as potent inhibitors of α-glucosidase, even better than standard drug Acarbose. Molecular modelling studies into the binding sites of α-glucosidase indicate the stable anchoring of 5p and 5r with favourable binding interactions. In addition, pharmacokinetic/dynamic attributes of compounds were estimated by using the ADMET profile. Graphical abstract: [Figure not available: see fulltext.]. © 2022, Institute of Chemistry, Slovak Academy of Sciences.