Synthesis and Biological Evaluation of Benzimidazoles as Target for α-Glucosidase Inhibitors
Diabetes mellitus is rising globally touching more than 180 million people worldwide. This is prevailing mostly in type 2 diabetes and according to WHO report the incidence is likely to be more than doubled by 2030. α-glucosidase inhibitors work by reducing the amount of glucose that the intestines absorb from food. In our previous work, forty-five benzimidazoles analogues were studied using 3D QSAR, HQSAR, and Pharmacophore mapping and based on their results 60 compounds were designed. Docking studies of those designed compounds showed that most of the compounds are bonding with important amino acids LEU 520, ARG 335 and ASP 69 through hydrogen bonds and steric interaction. In this work, synthesis of eleven compounds was done on the basis of molecular docking studies. Compounds containing hydroxyl and alkyl groups (compound no. 3, 9 and 10) were found to be five to eight folds more active with IC90 values in the range of 6.02 ± 1.10 to 33.25 ± 1.20 µg/ml, in comparison with the standard drug, Acarbose (IC90= 290.55 ± 0.081 µg/ml). Thus, these compounds after the toxicity studies could be of therapeutic use in treating diabetes.
Keywords: Acarbose, Alpha-glucosidase inhibition, Benzimidazoles, Docking, Molecular modelling, Post-prandial hyperglycemia
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