Synthesis and biological evaluation of novel 4-hydroxybenzaldehyde derivatives as tyrosinase inhibitors

Eur J Med Chem. 2010 Feb;45(2):639-46. doi: 10.1016/j.ejmech.2009.11.007. Epub 2009 Nov 10.

Abstract

A series of novel 4-hydroxybenzaldehyde derivatives were synthesized and their inhibitory effects on the diphenolase activity of mushroom tyrosinase were investigated. Most of target compounds had more potent inhibitory activities than the parent compound 4-hydroxybenzaldehyde (IC(50)=1.22 mM). Interestingly, compound 3c bearing a dimethoxyl phosphate was found to be the most potent inhibitor with IC(50) value of 0.059 mM. The inhibition kinetics analyzed by Lineweaver-Burk plots revealed that compound 3c was a non-competitive inhibitor (K(I)=0.0368 mM). In particular, compound 3c showed no side effects at dose of 1600 mg/kg in mice. These results suggested that such compounds might be served as lead compounds for further designing new potential tyrosinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / enzymology
  • Animals
  • Benzaldehydes / chemical synthesis*
  • Benzaldehydes / chemistry
  • Benzaldehydes / pharmacology*
  • Benzaldehydes / toxicity
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / toxicity
  • Inhibitory Concentration 50
  • Mice
  • Monophenol Monooxygenase / antagonists & inhibitors*

Substances

  • Benzaldehydes
  • Enzyme Inhibitors
  • Monophenol Monooxygenase
  • 4-hydroxybenzaldehyde