Inhibitory effects of novel synthetic methimazole derivatives on mushroom tyrosinase and melanogenesis

Bioorg Med Chem. 2014 May 1;22(9):2809-15. doi: 10.1016/j.bmc.2014.03.009. Epub 2014 Mar 15.

Abstract

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.

Keywords: Cytotoxicity; Kinetics; Melanin; Methimazole; Tyrosinase activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales
  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / toxicity
  • Kinetics
  • Melanins / metabolism*
  • Methimazole / chemical synthesis
  • Methimazole / chemistry*
  • Methimazole / toxicity
  • Mice
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism

Substances

  • Enzyme Inhibitors
  • Melanins
  • Methimazole
  • Monophenol Monooxygenase