Synthesis of benzimidazole based hydrazones as non-sugar based α-glucosidase inhibitors: Structure activity relation and molecular docking

In search for alpha-glucosidase inhibitors used in the treatment of diabetes mellitus, a series of unique benzimidazole based hydrazones derivatives were synthesized (5a-5p), which were then investigated for their in vitro alpha-glucosidase inhibitory potential. The compounds of interest were characterized by modern spectroscopic approaches including CHN, (HNM)-H-1 R, (CN)-C-13 MR and FTIR. The structure of compound 5n was distinctively authenticated through single crystal X-ray study. All compounds depicted potent enzyme inhibitory potential with IC50 values in the range of 2.25 +/- 0.01 to 81.16 +/- 0.12 mu M except 5n that showed IC50 value of 182.75 +/- 0.13 mu M. A limited structure-activity correlation demonstrated that substitutions of isatin, aldehydes and ketone in hydrazones moiety had remarkable contribution in the overall activity and that was further supported by molecular docking studies carried out in elucidating the mechanism of binding interaction of these compounds in the catalytic site of alpha-glucosidase.