Synthesis and biological evaluation of novel sesamol analogs targeting acetylcholinesterase, α-glycosidase, and carbonic anhydrase enzymes

This study describes the synthesis and biological evaluation of phenacyl-based sesamol derivatives as inhibitors of acetylcholinesterase (AChE), α-glycosidase (AG), and carbonic anhydrases I and II (CA I and II). The compounds were fully characterized by NMR and IR spectroscopy, and their inhibitory activities were assessed through enzyme assays and molecular docking. The derivatives showed potent inhibitory activity, with nanomolar Kᵢ values ranging from 1.25 to 4.04 nM for AChE, 11.14 to 45.48 nM for AG, 54.63 to 103.89 nM for CA I, and 30.90 to 104.17 nM for CA II. Compound 9 displayed potent AChE (IC50 = 7.00 nM) and CA II (IC50 = 46.21 nM) inhibition, while compounds 10 was the most active against AG (IC50 = 25.67 nM), and compound 10 showed the highest activity against CA I (IC50 = 49.51 nM). Docking studies supported the experimental findings and clarified key binding interactions. These findings suggest that the synthesized derivatives may have potential as lead compounds for drug development, particularly in the treatment of enzyme-related disorders, and provide a foundation for further research in this area.