Design, Synthesis, and Bioactivity Evaluation of Novel Phenol Derivatives Bearing a 1,2,4-Triazole Thioether Scaffold

In this study, using the plant-derived active compounds guaiacol and carvacrol as the lead structures, a series of novel phenol derivatives bearing an 1,2,4-triazole thioether scaffold were synthesized, and their structures were characterized by 1H, 13C NMR, and HRMS. The in vitro antioxidant and α-glucosidase inhibitory activities of these compounds were subsequently evaluated. Bioassay results demonstrated that the target compounds exhibited certain in vitro DPPH and ABTS scavenging as well as α-glucosidase inhibitory activities. Notably, 4-ethyl-3-[(5-isopropyl-2-methylphenoxy)methyl]-5-(propylthio)-4H-1,2,4-triazole displayed excellent in vitro α-glucosidase inhibitory activity, with an inhibition rate of 56.68%, surpassing that of the reference drug acarbose (53.00%). To the best of our knowledge, this is the first report on the synthesis and biological evaluation of this class of phenol derivatives bearing an 1,2,4-triazole thioether scaffold.