Design, synthesis, bioactivity evaluation, molecular docking, ADMET, and drug-likeness studies of novel thiochroman-4-one derivatives containing a semicarbazone moiety as potential α-glucosidase inhibitors

In this study, a series of novel thiochroman-4-one derivatives incorporating a semicarbazone functional group were successfully synthesized and thoroughly characterized via 1H NMR,13C NMR, and HRMS analyses. Biological evaluations revealed that the synthesized compounds 6a–6k exhibited moderate in vitro antioxidant effects, as demonstrated by their ability to scavenge DPPH and ABTS radicals, along with notable α-glucosidase inhibition. Among them, compound 6h stood out with significant in vitro inhibitory potency against α-glucosidase, yielding an IC50 value of 84.65 µg/mL, which was substantially lower than that of acarbose (237.48 µg/mL). The molecular docking analysis revealed that compound 6h interacts strongly with the active site of human intestinal α-glucosidase (PDB ID: 3TOP) via several binding interactions, exhibiting a binding energy of −8.6 kcal/mol. Moreover, the predicted ADMET properties and drug-likeness evaluation suggest that compound 6h possesses promising pharmacokinetic characteristics and a low toxicity risk, fulfilling essential requirements for prospective therapeutic candidates.