Synthesis and evaluation of 5-benzylidene(thio)barbiturate-beta-D-glycosides as mushroom tyrosinase inhibitors.

A series of 5-benzylidene(thio)barbiturate-beta-d-glycosides were designed, synthesized and evaluated as a new class of mushroom tyrosinase inhibitors. The results demonstrated that most of compounds had more potent inhibitory activities than arbutin (IC(50) 8.4mmol/L). Compound 12b was found to be the most potent inhibitor with IC(50) value of 0.05mmol/L. SARs analysis suggested that (1) 5-benzylidenethiobarbiturate substructures were efficacious for the inhibitory activity; (2) the lipophilic property of acetylated sugar moiety facilitated the inhibitory potency; (3) the hydroxyl group of 3'-configuration contributed to the increase of inhibitory effects. In addition, the inhibition mechanism study revealed that 5-benzylidene(thio)barbiturate-beta-d-glycosides were irreversible inhibitors.