Indole 3-heterocyclic derivative: A potential antioxidant, antidiabetic agent and their docking study on alpha amylase

Abstract

α-Amylase enzymes play a crucial role in breaking down starch molecules into simple sugar units that are easily absorbed into the bloodstream, resulting in a sudden increase in blood glucose levels. To respond this effect, there is a need for potent inhibitors that can hinder the enzymatic action of α-amylase. In this regard, indole-3-heterocycles (13−23) were synthesized via functionalizing of 3-(4-chlorobutyl)-1H-indole-5-carbonitrile with different triazoles, tetrazole, thiazole and mercapto benzothiazole with a base. Analytical techniques like 1H, 13C NMR, HRMS and IR spectroscopy characterized the newly synthesized indole heterocycles. These indole compounds functionalized were investigated for antidiabetic properties and antioxidant potentials on varying the side-chain. The synthesized indole compounds exhibited varying inhibition compared to α-amylase standard with IC50 values ranging between 6.44±1.14 μg/mL and 29.27±1.06 μg/mL competing with standard acarbose (IC50 = 5.7 ± 0.99 μg/mL). Among the series of eleven compounds, higher activity of IC50 = 6.44 ± 1.14 μg/mL was exhibited by compound 19 against α-amylase. In addition, an antioxidant potential of IC50 values of 15.62±1.20 μg/mL and 12.00 ± 1.00 μg/mL in 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and 2,2′-casino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays, respectively. The binding interactions of indole-3-heterocycles (13–23) were evaluated via in-silico docking performed on 5KEZ enzyme's active site. The current study has shown a light on the potential antidiabetic and antioxidant properties of lead molecules.