Novel synthetic kojic acid-methimazole derivatives inhibit mushroom tyrosinase and melanogenesis

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• 作者：Ming-Jen Chen ; Chih-Chuan Hung ; Yan-Ru Chen ; Shih-Ting Lai ; Chin-Feng Chan ; ^{cfchanjames@hotmail.com}
• 关键词：Kojic acid ; Methimazole ; Mushroom tyrosinase ; Kinetics ; Melanin
• 刊名：Journal of Bioscience and Bioengineering
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：122
• 期：6
• 页码：666-672
• 全文大小：675 K
• 卷排序：122

文摘

In this study, two kojic acid-methimazole (2-mercapto-1-methylimidazole, MMI, 1) derivatives, 5-hydroxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 4) and 5-methoxy-2-{[(1-methyl-1H-imidazol-2-yl)thio]methyl}-4H-pyran-4-one (compound 5), were synthesized to examine their inhibitory kinetics on mushroom tyrosinase. Compound 4 exhibited a potent inhibitory effect on monophenolase activity in a dose-dependent manner, with an IC50 value of 0.03 mM. On diphenolase activity, compound 4 exhibited a less inhibitory effect (IC50 = 1.29 mM) but was stronger than kojic acid (IC50 = 1.80 mM). Kinetic analysis indicated that compound 4 was both as a noncompetitive monophenolase and diphenolase inhibitor. By contrast, compound 5 exhibited no inhibitory effects on mushroom tyrosinase activity. The IC50 value of compound 4 for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was 4.09 mM, being much higher than the IC50 of compound 4 for inhibiting the tyrosinase activity. The results indicated that the antioxidant activity of compound 4 may be partly related to the potent inhibitory effect on mushroom tyrosinase. Compound 4 also exerted a potent inhibitory effect on intracellular melanin formation in B16/F10 murine melanoma cells, and caused no cytotoxicity. Furthermore, compound 4 induced no adverse effects on the Hen's egg test-chorioallantoic membrane (HET-CAM).