New phenyl γ-butyrolactone glucosides derived from γ-irradiation of esculin in methanol exhibit significant α-glucosidase inhibitory activity.

Esculin, a coumarin glucoside, was subjected to γ-irradiation in methanolic solution to afford two novel γ-lactone derivatives, compounds 2 and 3. The structures of the newly generated compounds 2 and 3 were identified using spectroscopic methods, including nuclear magnetic resonance and mass spectrometry. Compound 2, featuring an additional hydroxymethyl substituent on the γ-butyrolactone scaffold, exhibited significantly enhanced α-glucosidase inhibitory activity (IC50 = 36.0 ± 1.0 µM) compared with the parent esculin (IC50 = 147.8 ± 2.5 µM). Enzyme kinetic studies confirmed that both compounds function as competitive inhibitors, with 2 exhibiting the lowest Ki value (32.1 ± 0.9 µM). These findings demonstrate that γ-irradiation is an effective one-step strategy for generating biologically active γ-lactone derivatives from natural coumarin glycosides and highlight its potential for the development of novel non-sugar-based hypoglycemic agents.