Chromenone Coupled to Spiro[Indene-2,3′-Pyrrolizine]-1,3-Diones As a Novel Class of Α-Glucosidase Inhibitor Publisher Pubmed



Eisayi A ; Fathi A ; Ramezanpour S ; Eftekharian F ; Dastyafteh N ; Mahdavi M ; Iraji A ; Darvish F
Source: Bioorganic Chemistry Published:2026

Abstract

This study reported the design and synthesis of a new series of chromenone-linked spiro[indene-2,3′-pyrrolizine]-1,3-dione derivatives as α-glucosidase inhibitors. The target compounds were synthesized using a three-step process, including Pechmann condensation, aldol condensation, and 1,3-dipolar cycloaddition, with high yields. In vitro tests showed promising α-glucosidase inhibitory activities of derivatives, with compound 3m (3-bromo derivative) being the most potent analog, having an IC50 of 45.07 ± 7.54 μM, approximately 16 times more potent than acarbose. Additionally, kinetic studies were also conducted. Molecular docking and 100 ns molecular dynamics simulations confirmed stable interactions with key residues, shown by low RMSD and RMSF values. These findings provide preliminary evidence of α-glucosidase inhibitory activities of chromenone-spiro[indene-2,3′-pyrrolizine]-1,3-dione derivative. Copyright © 2026. Published by Elsevier Inc.