title: Novel synthetic kojic acid-methimazole derivatives inhibit mushroom tyrosinase and melanogenesis.
abstract: 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 IC50value 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 IC50value of compound 4 for the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity was 4.09 mM, being much higher than the IC50of 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).
authors.affiliation: Department of Applied Cosmetology, Hungkuang University, Taichung, Taiwan.
authors.forename: Ming-Jen
authors.initials: MJ
authors.lastname: Chen
authors.affiliation: Department of Applied Cosmetology, Hungkuang University, Taichung, Taiwan.
authors.forename: Chih-Chuan
authors.initials: CC
authors.lastname: Hung
authors.affiliation: Department of Applied Cosmetology, Hungkuang University, Taichung, Taiwan.
authors.forename: Yan-Ru
authors.initials: YR
authors.lastname: Chen
authors.affiliation: Department of Applied Cosmetology, Hungkuang University, Taichung, Taiwan.
authors.forename: Shih-Ting
authors.initials: ST
authors.lastname: Lai
authors.affiliation: Department of Applied Cosmetology, Hungkuang University, Taichung, Taiwan. Electronic address: cfchanjames@hotmail.com.
authors.forename: Chin-Feng
authors.initials: CF
authors.lastname: Chan
mesh_terms: D000363:Agaricales / Q000201:enzymology*; D000818:Animals; D001713:Biphenyl Compounds / Q000737:chemistry; D002642:Chick Embryo; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D008543:Melanins / Q000096:biosynthesis*; D008546:Melanoma, Experimental / Q000473:pathology; D008713:Methimazole / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010851:Picrates / Q000737:chemistry; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012878:Skin Neoplasms / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D008543:Melanins; D010851:Picrates; D011753:Pyrones; D008713:Methimazole; C011890:kojic acid; C004931:1,1-diphenyl-2-picrylhydrazyl; D014442:Monophenol Monooxygenase
keywords: Kinetics; Kojic acid; Melanin; Methimazole; Mushroom tyrosinase