Depigmenting activity and low cytotoxicity of alkoxy benzoates or alkoxy cinnamte in cultured melanocytes.
To obtain effective and safe topical depigmenting agents, we synthesized hydroxybenzoates, alkoxybenzoates, and 3,4,5-trimethoxycinnamate containing a thymol moiety and screened then for high-level inhibitory activity against melanin synthesis in cultured melanocytes. Eight compounds were tested for their depigmenting effect and cytotoxicity using a murine melanocyte cell line. We found that 3,4,5-trialkoxybenzoates and 3,4,5-trimethoxycinnamate, synthesized by conjugating 3,4,5-trialkoxybenzoic acids and 3,4,5-trimethoxycinnmic acid with thymol, showed a potent depigmenting effect and low cytotoxicity. Compound 4h, 5-methyl-2-(methylethyl)phenyl (2E)-3-(3,4,5-trimethoxyphenyl)prop-2-enoate, showed the most potent depigmenting effect (IC50=10 microM) with low cytotoxicity (IC50=200 microM).
Kang
Hak Hee
HH
Department of Chemical Engineering, College of Engineering, Hanyang University, Seoul, Korea.
Rho
Ho Sik
HS
Hwang
Jae Sung
JS
Oh
Seong-Geon
SG
D000818:Animals; D001565:Benzoates / Q000494:pharmacology* / Q000633:toxicity; D001713:Biphenyl Compounds; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002934:Cinnamates / Q000494:pharmacology* / Q000633:toxicity; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008543:Melanins / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors; D010851:Picrates / Q000737:chemistry; D010858:Pigmentation / Q000187:drug effects*; D013055:Spectrophotometry, Infrared
D001565:Benzoates; D001713:Biphenyl Compounds; D002934:Cinnamates; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D008543:Melanins; D010851:Picrates; C004931:1,1-diphenyl-2-picrylhydrazyl; D014442:Monophenol Monooxygenase