Evaluation of the anti-diabetic activity of triaryl benzimidazole compounds, in vitro and molecular dynamic simulation study

A series of benzimidazole-based triazolo-thiadiazole derivatives ( 1–20 ) were synthesized and evaluated for their inhibitory activity against α -glucosidase and α -amylase to assess their antidiabetic potential. All synthesized compounds were characterized by Nuclear Magnetic Resonance Spectroscopy and High Resolution-Electron Ionization Mass Spectrometry. All analogs showed excellent inhibitory potential for both enzymes. The most potent compound among the series is analog 5 , having dihydroxy substitution on phenyl ring showed excellent inhibition for α -amylase with (IC 50 = 0.4 ± 0.1 µM) and α -glucosidase (IC 50 = 0.6 ± 0.1 µM) when compared with standard drug acarbose (IC 50 = 10.4 ± 0.1 µM and 10.4 ± 0.1 µM) respectively. Structure activity relationships have been established for all compounds. Further molecular docking study was performed to understand the binding interaction between potent molecules and enzyme active site. The results were strengthened by performing molecular docking studies of most potent compounds 4, 5 , and 12 with the binding affinity −12.12 kcal/mol, −13.25 kcal/mol, −12.90 kcal/mol.