Chromenone coupled to spiro[indene-2,3'-pyrrolizine]-1,3-diones as a novel class of α-glucosidase inhibitor

Bioorg Chem. 2026 Jul 15:176:109739. doi: 10.1016/j.bioorg.2026.109739. Epub 2026 Mar 19.

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.

Keywords: Molecular dynamics simulations; Pechmann condensation; Spiro[indene-2,3′-pyrrolizine]-1,3-dione; α-Glucosidase.

MeSH terms

  • Benzopyrans* / chemistry
  • Benzopyrans* / pharmacology
  • Dose-Response Relationship, Drug
  • Glycoside Hydrolase Inhibitors* / chemical synthesis
  • Glycoside Hydrolase Inhibitors* / chemistry
  • Glycoside Hydrolase Inhibitors* / pharmacology
  • Molecular Docking Simulation
  • Molecular Dynamics Simulation
  • Molecular Structure
  • Spiro Compounds* / chemical synthesis
  • Spiro Compounds* / chemistry
  • Spiro Compounds* / pharmacology
  • Structure-Activity Relationship
  • alpha-Glucosidases* / metabolism

Substances

  • Glycoside Hydrolase Inhibitors
  • alpha-Glucosidases
  • Spiro Compounds
  • Benzopyrans