Synthetic tyrosyl gallate derivatives as potent melanin formation inhibitors.
Three tyrosyl gallate derivatives (1-3) with variable hydroxyl substituent at the aromatic ring of tyrosol were synthesized and evaluated as potent inhibitors on tyrosinase activity and melanin formation in melan-a cells. Among three tyrosyl gallate derivatives, 4-hydroxyphenethyl 3,4,5-trihydroxybenote (1) (IC(50)=4.93 microM), 3-hydroxyphenethyl 3,4,5-trihydroxybenote (2) (IC(50)=15.21 microM), and 2-hydroxyphenethyl 3,4,5-trihydroxybenote (3) (IC(50)=14.50 microM) exhibited significant inhibitory effect on tyrosinase activity. Compound 1 was the most active compound, though it did not show the inhibitory effect on melanin formation in melan-a cells. However, compounds 2 (IC(50)=8.94 microM) and 3 (IC(50)=13.67 microM) significantly suppressed the cellular melanin formation without cytotoxicity. This study shows that the position of hydroxyl substituent at the aromatic ring of tyrosol plays an important role in the intracellular regulation of melanin formation in cell-based assay system.
Lee
Chan Woo
CW
R&D Center, AmorePacific Corporation, Kyounggi-do 449-729, Republic of Korea.
Son
Eun-Mi
EM
Kim
Han Sung
HS
Xu
Pan
P
Batmunkh
Tuyagerel
T
Lee
Burm-Jong
BJ
Koo
Kyung Ah
KA
D002384:Catalysis; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*
D008543:Melanins; D014443:Tyrosine; D005707:Gallic Acid; D014442:Monophenol Monooxygenase