Inhibitory effects of 1,3-thiazine derivatives on melanogenesis

J Pharm Pharmacol. 2009 Dec;61(12):1657-63. doi: 10.1211/jpp/61.12.0011.

Abstract

Objectives: The aim of this study was to identify a novel skin-depigmenting agent from synthetic 1,3-thiazine derivatives.

Methods: We investigated the inhibitory effects of six kinds of 1,3-thiazine derivative on melanogenesis by examining their effects on tyrosinase activity and melanin biosynthesis in melan-a cells and the zebrafish model.

Key findings: Of the six compounds, 4-hydroxy-2,6-dimethyl-5,6-dihydro-4H-1,3-thiazine (TZ-6) had the strongest anti-melanogenic effects in cultured melan-a cells (30.4% inhibition at 100 microm). In addition, TZ-6 exhibited an inhibitory effect on mushroom and cellular tyrosinase. Based on the results of Western blotting, TZ-6 reduced the expression of tyrosinase at 100 microm. Additionally, TZ-6 reduced body pigmentation and inhibited tyrosinase activity in the zebrafish model.

Conclusions: The results have provided useful information for the development of a skin whitening agent.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry
  • Animals
  • Cells, Cultured
  • Enzyme Inhibitors / pharmacology*
  • Melanins / biosynthesis*
  • Melanocytes / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Skin / drug effects*
  • Skin / metabolism
  • Skin Pigmentation / drug effects*
  • Thiazines / isolation & purification
  • Thiazines / pharmacology*
  • Zebrafish

Substances

  • 4-hydroxy-2,6-dimethyl-5,6-dihydro-4H-1,3-thiazine
  • Enzyme Inhibitors
  • Melanins
  • Thiazines
  • Monophenol Monooxygenase