Discovery of 3,3-di(indolyl)indolin-2-one as a novel scaffold for α-glucosidase inhibitors: In silico studies and SAR predictions

Abstract

3,3-Di(indolyl)indolin-2-ones 4a-4n were synthesized and evaluated for their in vitro α-glucosidase inhibitory activity. These newly synthesized compounds showed moderate to potent α-glucosidase inhibitory activity with IC₅₀ range from 5.98±0.11 to 145.95±0.46μM, when compared to the standard drug acarbose. Among this series of 3,3-di(indolyl)indolin-2-ones, compound 4j(5.98±0.11μM) having a 2-fluorobenzyl group on the indole ring was found to be the most active compound. Molecular docking studies showed that compound 4j have high binding affinities with the active site of α-glucosidase enzyme through hydrogen bonds, arene-cation, π-π stacking and hydrophobic interactions. This study showed these 3,3-di(indolyl)indolin-2-ones as a new class of α-glucosidase inhibitors.

Keywords: 3,3-Diaryloxindoles; Indole; Molecular docking; Oxindole; α-Glucosidase inhibitor.