Design, synthesis docking and molecular dynamics studies of 2-amino-4-- phenylthiazole-indole hybrids as -glucosidase inhibitors

In our effort directed toward the development of novel alpha-glucosidase inhibitors by molecular hybridization theory, a novel series of 2-amino-4-phenylthiazole-indole hybrids 7a-l was designed, synthesized, and evaluated. Our in vitro results demonstrated that all these compounds (7a-l) were more potent than positive control acarbose. Kinetic study of the most active entry (compound 7i) was also carried out to determine the mode of inhibition. The latter study revealed that compound 7i was a competitive inhibitor against alpha-glucosidase. Furthermore, the binding interaction modes of the most active compounds within the alpha-glucosidase active site were studied by molecular docking. Moreover, molecular dynamics of compound 7i was also carried out in order to determine the stability of complex compound 7i-alpha-glucosidase. The in silico pharmacokinetics and toxicity studies of the most potent compounds predicted that these compounds can be consider as useful lead structures to obtain new anti-diabetic agents.