Inhibitory effects of novel synthetic methimazole derivatives on mushroom tyrosinase and melanogenesis.
In this study, we synthesized 4 methimazole (2-mercapto-1-methylimidazole, MMI) derivatives. The kinetics of inhibition on mushroom tyrosinase by methimazole and its derivatives were investigated. The results indicated that tert-butyl 3-methyl-2-sulfanylidene-2,3-dihydro-1H-imidazole-1-carboxylate (compound 3; 3), 2-mercaptoimidazole (MI; compound 1; 1) and MMI (compound 2; 2) significantly inhibited tyrosinase activity in a dose-dependent manner, exhibiting an IC50 value of 1.50mM, 4.11 mM, and 1.43 mM. However, compound 4 (4), compound 5 (5), and compound 6 (6) exerted no inhibitory effect on mushroom tyrosinase activity. Kinetic analysis indicated that 3 was a noncompetitive tyrosinase inhibitor, whereas both 1 and 2 were exhibited as mixed-type tyrosinase inhibitors. Furthermore, 3 exerted a potent inhibitory effect on intracellular melanin formation in the B16/F10 murine melanoma cells and did not cause cytotoxicity, as 1 and 2 did.
Department of Applied Cosmetology, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung 43302, Taiwan. Electronic address: cfchanjames@hotmail.com.
Chin-Feng
CF
Chan
Department of Applied Cosmetology, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung 43302, Taiwan.
Shih-Ting
ST
Lai
Department of Applied Cosmetology, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung 43302, Taiwan.
Yi-Cin
YC
Guo
Department of Applied Cosmetology, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung 43302, Taiwan. Electronic address: mjchen@hk.edu.tw.
Ming-Jen
MJ
Chen
D000363:Agaricales; D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D007700:Kinetics; D008543:Melanins / Q000378:metabolism*; D008713:Methimazole / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D004791:Enzyme Inhibitors; D008543:Melanins; D008713:Methimazole; D014442:Monophenol Monooxygenase
Cytotoxicity; Kinetics; Melanin; Methimazole; Tyrosinase activity