Dicyanoanilines as potential and dual inhibitors of α-amylase and α-glucosidase enzymes: Synthesis, characterization, in vitro, in silico, and kinetics studies

The present study comprised of the synthesis of dicyanoaniline derivatives of pyridine, thiophene, furan, and substituted phenyl 1-29. All synthetic derivatives were evaluated for their potential to inhibit alpha-amylase and alpha-glucosidase enzymes. The synthesized compounds are classified into three categories A, B, and C based on variable substituents at R-1 and R-2, and the structure-activity relationship was discussed accordingly. Amongst twenty-nine derivatives, 1-29, five compounds 2, 9, 18, 23, and 24 displayed excellent inhibition against alpha-amylase and a-glucosidase enzymes with the IC50 values ranging between 20.33 +/- 0.02-25.50 +/- 0.06 mM and 21.01 +/- 0.1 2-27.75 +/- 0.17 mM, respectively, while other compounds showed moderate to weak inhibition against both enzymes. Acarbose was used as the positive control in this study. The enzyme kinetic studies showed non-competitive and un-competitive types of inhibition mechanism against alpha-amylase and alpha-glucosidase enzymes, respectively. In silico studies have demonstrated the involvement of these molecules in numerous binding interactions within the active site of the enzyme. (C) 2021 The Author(s). Published by Elsevier B.V. on behalf of King Saud University.

Automated summary

The study focuses on the synthesis of dicyanoaniline derivatives and their inhibition activities against alpha-amylase and alpha-glucosidase enzymes. Among the synthesized compounds, five of them showed excellent inhibition against the enzymes. Enzyme kinetic studies revealed different types of inhibition mechanisms, and computer simulations demonstrated the involvement of these molecules in binding interactions at the enzyme's active site.