Indole-pyridine carbonitriles: multicomponent reaction synthesis and bio-evaluation as potential hits against diabetes mellitus

Abstract

Background: Diabetes mellitus is a significant health disorder; therefore, researchers should focus on discovering new drug candidates. Methods: A series of indole-pyridine carbonitrile derivatives, 1-34, was synthesized through a one-pot multicomponent reaction and evaluated for antidiabetic and antioxidant potential. Results: In this library, 12 derivatives - 1, 2, 4, 5, 7, 8, 10-12, 14, 15 and 31 - exhibited potent inhibitory activities against α-glucosidase and α-amylase enzymes, in comparison to acarbose (IC50 = 14.50 ± 0.11 μM). Furthermore, kinetics, absorption, distribution, metabolism, excretion and toxicity and molecular docking studies were used to interpret the type of inhibition, binding energies and interactions of ligands with target enzymes. Conclusion: These results indicate that the compounds may be promising hits for controlling diabetes mellitus and its related complications.