Discovery of 4-functionalized phenyl-O-beta-D-glycosides as a new class of mushroom tyrosinase inhibitors.
A series of 4-functionalized phenyl-O-beta-D-glycosides were designed, synthesized and evaluated as a new class of mushroom tyrosinase inhibitors. The results demonstrated that compounds 6a-13a bearing a thiosemicarbazide moiety exhibited potent activities with IC50 values range from 0.31 to 52.8 microM. Particularly, compound 9a containing acetylated glucose moiety was found to be the most active molecule with an IC50 value of 0.31 microM. SARs analysis suggested that (1) the thiosemicarbazide moiety remarkably contributed to the increase of inhibitory effects on tyrosinase; (2) the configuration and bond type of sugar moiety also played a very important role in determining their inhibitory activities. The inhibition kinetics and inhibition mechanism study revealed that compound 9a was reversible and competitive type inhibitor, whereas compound 13a was reversible and competitive-uncompetitive mixed-II type inhibitor.
Yi
Wei
W
School of Chemistry and Chemical Engineering, Sun Yat-sen University, 135 Xin Gang West Road, Guangzhou 510275, PR China.
Cao
Rihui
R
Wen
Huan
H
Yan
Qin
Q
Zhou
Binhua
B
Ma
Lin
L
Song
Huacan
H
D000363:Agaricales / Q000201:enzymology*; D015195:Drug Design; D005960:Glucosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006027:Glycosides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012663:Semicarbazides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D005960:Glucosides; D006027:Glycosides; D010455:Peptides; D012663:Semicarbazides; C005151:thiosemicarbazide; D014442:Monophenol Monooxygenase