Synthesis and evaluation of 2',4',6'-trihydroxychalcones as a new class of tyrosinase inhibitors.
In this study, we synthesized a series of hydroxychalcones and examined their tyrosinase inhibitory activity. The results showed that 2',4',6'-trihydroxychalcone (1), 2,2',3,4',6'-pentahydroxychalcone (4), 2',3,4,4',5,6'-hexahydroxychalcone (5), 2',4',6'-trihydroxy- 3,4-dimethoxychalcone (9) and 2,2',4,4',6'-pentahydroxychalcone (15) exhibited high inhibitory effects on tyrosinase with respect to l-tyrosine as a substrate. By the structure-activity relationship study, it was suggested that the 2',4',6'-trihydroxyl substructure in the chalcone skeleton were efficacious for the inhibition of tyrosinase activity. And also, the catechol structure on B-ring of chalcones was not advantageous for the inhibitory potency. Furthermore, 15 (IC(50)=1microM) was found to show the highest activity out of a set of 15 hydroxychalcones, even better than both 2,2',4,4'-tetrahydroxychalcone (13, IC(50)=5microM) and kojic acid (16, IC(50)=12microM), which were known as potent tyrosinase inhibitors. Kinetic study revealed that 15 acts as a competitive inhibitor of tyrosinase with K(i) value of 3.1microM.
Jun
Nishida
N
Division of Applied Bioscience, Graduate School of Agriculture, Hokkaido University, Kita-ku, Sapporo 060-8589, Japan.
Hong
Gao
G
Jun
Kawabata
K
D000363:Agaricales / Q000201:enzymology; D047188:Chalcones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D047188:Chalcones; D004791:Enzyme Inhibitors; D010455:Peptides; C117518:pinocembrin chalcone; D014442:Monophenol Monooxygenase