Introduction of new quinolone-2-thio-acetamide-propane hydrazide-benzimidazole derivatives as new α-glucosidase and α-amylase inhibitors

Abstract

In the present work, new quinolone-2-thio-acetamide-propane hydrazide-benzimidazole derivatives 12a-o were assigned as potent anti-diabetic agents that targeting alpha-glucosidase and alpha-amylase as two important targets in treatment of type 2 diabetes. General scaffold of these compounds was designed based on the reported potent alpha-glucosidase and alpha-amylase inhibitors and derivation was performed in acetamide moiety. In vitro evaluation of the new compounds 12a-o demonstrated that most of the synthesized compounds were more potent than standard inhibitor acarbose against alpha-glucosidase while all these new compounds were more potent than acaerbose against alpha-amylase. The most potent compound against both studied enzymes was compound 12n that was a 4-fluorophenylacetamide derivative. This compound was 5 and 23.8 folds more potent than acarbose against alpha-glucosidase and alpha-amylase, respectively, and with excellent binding energies in comparison to acarbose attached to active sites of these enzymes. Molecular dynamics and pharmacokinetic studies of compound 12n was also performed.