Synthesis of azachalcones, their α-amylase, α-glucosidase inhibitory activities, kinetics, and molecular docking studies

Abstract

Diabetes being a chronic metabolic disorder have attracted the attention of medicinal chemists and biologists. The introduction of new and potential drug candidates for the cure and treatment of diabetes has become a major concern due to its increased prevelance worldwide. In the current study, twenty-seven azachalcone derivatives 3-29 were synthesized and evaluated for their antihyperglycemic activities by inhibiting α-amylase and α-glucosidase enzymes. Five compounds 3 (IC₅₀ = 23.08 ± 0.03 µM), (IC₅₀ = 26.08 ± 0.43 µM), 5 (IC₅₀ = 24.57 ± 0.07 µM), (IC₅₀ = 27.57 ± 0.07 µM), 6 (IC₅₀ = 24.94 ± 0.12 µM), (IC₅₀ = 27.13 ± 0.08 µM), 16 (IC₅₀ = 27.57 ± 0.07 µM), (IC₅₀ = 29.13 ± 0.18 µM), and 28 (IC₅₀ = 26.94 ± 0.12 µM) (IC₅₀ = 27.99 ± 0.09 µM) demonstrated good inhibitory activities against α-amylase and α-glucosidase enzymes, respectively. Acarbose was used as the standard in this study. Structure-activity relationship was established by considering the parent skeleton and different substitutions on aryl ring. The compounds were also subjected for kinetic studies to study their mechanism of action and they showed competitive mode of inhibition against both enzymes. The molecular docking studies have supported the results and showed that these compounds have been involved in various binding interactions within the active site of enzyme.

Keywords: Antihyperglycemic; Azachalcones; Enzyme inhibition; Kinetics; Molecular docking study; Pyridine.