N-[(Dihydroxyphenyl)acyl]serotonins as potent inhibitors of tyrosinase from mouse and human melanoma cells.
A series of N-acyl derivatives of tyramine, tryptamine, and serotonin were synthesized and tested on anti-melanogenic activity. The serotonin derivatives such as N-caffeoylserotonin (3) and N-protocatechuoylserotonin (9) were inhibitory to tyrosinase from mouse B16 and human HMV-II melanoma cells, while the corresponding derivatives of tryptamine and 5-methoxytryptamine were almost inactive or less active than the serotonin derivatives. The inhibitory activity of the serotonin derivatives increased with increasing number of phenolic hydroxyl groups in the acyl moiety. Melanin formation in the culture of B16 cells was suppressed by 3 and 9 with no cytotoxicity in the concentration range tested (IC(50)=15, 3 and 111muM for 3, 9, and kojic acid, respectively). Thus the N-acylserotonin derivatives having a dihydroxyphenyl group are potential anti-melanogenic agents. Their inhibition of tyrosinase is primarily performed through the 5-hydroxyindole moiety and further strengthened by the phenolic hydroxyl groups in the acyl moiety.
Yamazaki
Yoshimitsu
Y
Institute for Biological Resources and Functions, National Institute of Advanced Industrial Science and Technology, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan. y.yamazaki@aist.go.jp
Kawano
Yasuhiro
Y
Yamanaka
Akiko
A
Maruyama
Susumu
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D008545:Melanoma / Q000188:drug therapy*; D008546:Melanoma, Experimental; D051379:Mice; D008956:Models, Chemical; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000737:chemistry; D019800:Phenol / Q000737:chemistry; D010636:Phenols / Q000138:chemical synthesis* / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry; D012701:Serotonin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D010636:Phenols; D011753:Pyrones; D012701:Serotonin; D019800:Phenol; C011890:kojic acid; D014442:Monophenol Monooxygenase