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.
Yan
Qin
Q
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Cao
Rihui
R
Yi
Wei
W
Yu
Liang
L
Chen
Zhiyong
Z
Ma
Lin
L
Song
Huacan
H
D000363:Agaricales / Q000187:drug effects* / Q000201:enzymology*; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D007980:Levodopa / Q000737:chemistry; D051379:Mice; D008956:Models, Chemical; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D006027:Glycosides; D010455:Peptides; D007980:Levodopa; D014442:Monophenol Monooxygenase