Design, synthesis, and evaluation of (E)-N-substituted benzylidene-aniline derivatives as tyrosinase inhibitors

Eur J Med Chem. 2012 Nov:57:383-90. doi: 10.1016/j.ejmech.2012.09.026. Epub 2012 Sep 23.

Abstract

We attempted to design and synthesize (E)-N-substituted benzylidene-hydroxy or methoxy-aniline derivatives and to evaluate their inhibitory effect on tyrosinase activity and anti-melanogenesis activity in murine B16F10 melanoma cells. Derivatives with a 4-methoxy- or 4-hydroxy-anilino group exerted more potent inhibition against mushroom tyrosinase than those with a 2-hydroxyanilino group. (E)-4-((4-Hydroxyphenylimino)methyl)benzene-1,2-diol exhibited the most potent and non-competitive inhibition on mushroom tyrosinase showing an IC(50) of 17.22 ± 0.38 μM and being more effective than kojic acid (51.11 ± 1.42 μM). This compound decreased melanin production stimulated by the alpha-melanocyte-stimulating hormone and inhibited murine tyrosinase activity in a dose-dependent manner. Therefore, we propose (E)-4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol as a new candidate of potent tyrosinase inhibitors that could be used as therapeutic agent with safe skin-whitening efficiency.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / chemistry
  • Aniline Compounds / chemistry*
  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Benzylidene Compounds / chemical synthesis*
  • Benzylidene Compounds / pharmacology
  • Catechols / chemical synthesis*
  • Catechols / pharmacology
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Assays
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Fungal Proteins / antagonists & inhibitors*
  • Fungal Proteins / metabolism
  • Kinetics
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis
  • Melanoma, Experimental / drug therapy
  • Melanoma, Experimental / enzymology
  • Mice
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Pyrones / pharmacology
  • Schiff Bases / chemical synthesis*
  • Schiff Bases / pharmacology
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / enzymology
  • Tumor Cells, Cultured
  • alpha-MSH / pharmacology

Substances

  • 4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol
  • Aniline Compounds
  • Antineoplastic Agents
  • Benzylidene Compounds
  • Catechols
  • Enzyme Inhibitors
  • Fungal Proteins
  • Melanins
  • Pyrones
  • Schiff Bases
  • alpha-MSH
  • kojic acid
  • Monophenol Monooxygenase
  • aniline