α-Amylase inhibitory potential of dihydropyrano coumarins: In silico and DFT analysis

3 Biotech. 2025 Feb;15(2):38. doi: 10.1007/s13205-024-04194-1. Epub 2025 Jan 11.

Abstract

Coumarin derivatives are one of the naturally occurring bioactive molecule. Dihydropyrano coumarins are one of the medicinally important derivatives of coumarin which have been reported to exhibit various bioactivity. However, there are no reports on their antihyperglycemic activities. Herein, we report their antihyperglycemic potential through α-Amylase inhibition. In this study, a series of 24 derivatives of dihydropyrano coumarins was synthesized and studied for alpha-Amylase inhibitory activity. All the derivatives of dihydropyrano coumarins (4a-x) were screened via molecular docking studies against human pancreatic alpha-Amylase (PDB id: 2QV4) followed by DNS assay to check their α-Amylase inhibitory potential. Six derivatives with o-chloro(4b), o-nitro(4c), p-nitro(4o), p-cyano(4q), p-allyloxy(4t) and m, p-dimethoxy(4v) displayed best binding with the α-Amylase enzyme via H-bond and Pi-alkyl interactions. Also, their physicochemical parameters revealed their drug likeliness. Further through DNS assay, minimal inhibitory concentration, i.e., IC50 values of these six derivatives were calculated. All the six derivatives possess IC50 values in the range 5.67 ± 0.02 to 8.92 ± 0.64 µM comparable to standard acarbose (0.85 ± 0.01 µM). Further DFT analysis gave a comparative study of band gap energy of most potent compound 4o with that of standard acarbose.

Supplementary information: The online version contains supplementary material available at 10.1007/s13205-024-04194-1.

Keywords: Antidiabetics; DFT analysis; Dihydropyrano coumarins; Molecular docking; α-Amylase inhibitor.