One of the most prevailing metabolic disorder diabetes mellitus has become the global health issue that has to be addressed and cured. Different marketed drugs have been made available for the treatment of diabetes but there is still a need of introducing new therapeutic agents that are economical and have lesser or no side effects. The current study deals with the synthesis of indole acrylonitriles (3-23) and the evaluation of these compounds for their potential for α-glucosidase inhibition. The structures of these synthetic molecules were deduced by using different spectroscopic techniques. Acarbose (IC50 = 2.91 ± 0.02 μM) was used as standard in this study and the synthetic molecules (3-23) have shown promising α-glucosidase inhibitory activity. Compounds 4, 8, 10, 11, 14, 18, and 21 displayed superior inhibition of α-glucosidase enzyme in the range of (IC50 = 0.53 ± 0.01-1.36 ± 0.04 μM) as compared to the standard acarbose. Compound 10 (IC50 = 0.53 ± 0.01 μM) was the most effective inhibitor of this library and displayed many folds enhanced activity in contrast to the standard. Molecular docking of synthetic compounds was performed to verify the binding interactions of ligand with the active site of enzyme. This study had identified a number of potential α-glucosidase inhibitors that can be used for further research to identify a potent therapeutic agent against diabetes.
A two-step reaction method was used to synthesize a series of rhodanine-based Schiff bases (2-33) that were characterized using spectroscopic techniques. All compounds were assessed for α-amylase inhibitory and radical scavenging (DPPH and ABTS) activities. In comparison to the standard acarbose (IC50 = 9.08 ± 0.07 µM), all compounds demonstrated good to moderate α-amylase inhibitory activity (IC50 = 10.91 ± 0.08-61.89 ± 0.102 µM). Compounds also demonstrated significantly higher DPPH (IC50 = 10.33 ± 0.02-96.65 ± 0.03 µM) and ABTS (IC50 = 12.01 ± 0.12-97.47 ± 0.13 µM) radical scavenging activities than ascorbic acid (DPPH, IC50 = 15.08 ± 0.03 µM; ABTS, IC50 = 16.09 ± 0.17 µM). The limited structure-activity relationship (SAR) suggests that the position and nature of the substituted groups on the phenyl ring have a vital role in varying inhibitory potential. Among the series, compounds with an electron-withdrawing group at the para position showed the highest potency. Kinetic studies revealed that the compounds followed a competitive mode of inhibition. Molecular docking results are found to agree with experimental findings, showing that compounds reside in the active pocket due to the main rhodanine moiety.