新型合成甲巯咪唑衍生物对蘑菇酪氨酸酶和黑色素生成的抑制作用。
Inhibitory effects of novel synthetic methimazole derivatives on mushroom tyrosinase and melanogenesis.
作者信息
Chan Chin-Feng, Lai Shih-Ting, Guo Yi-Cin, Chen Ming-Jen
机构信息
Department of Applied Cosmetology, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung 43302, Taiwan.
Department of Applied Cosmetology, Hungkuang University, No. 1018, Sec. 6, Taiwan Boulevard, Shalu District, Taichung 43302, Taiwan.
出版信息
Bioorg Med Chem. 2014 May 1;22(9):2809-15. doi: 10.1016/j.bmc.2014.03.009. Epub 2014 Mar 15.
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.
在本研究中，我们合成了4种甲巯咪唑（2-巯基-1-甲基咪唑，MMI）衍生物。研究了甲巯咪唑及其衍生物对蘑菇酪氨酸酶的抑制动力学。结果表明，3-甲基-2-亚硫酰基-2,3-二氢-1H-咪唑-1-羧酸叔丁酯（化合物3；3）、2-巯基咪唑（MI；化合物1；1）和MMI（化合物2；2）以剂量依赖性方式显著抑制酪氨酸酶活性，IC50值分别为1.50 mM、4.11 mM和1.43 mM。然而，化合物4（4）、化合物5（5）和化合物6（6）对蘑菇酪氨酸酶活性没有抑制作用。动力学分析表明，3是一种非竞争性酪氨酸酶抑制剂，而1和2均表现为混合型酪氨酸酶抑制剂。此外，3对B16/F10小鼠黑色素瘤细胞内黑色素的形成具有显著抑制作用，且不像1和2那样具有细胞毒性。
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