Synthesis and biological evaluation of novel hydroxybenzaldehyde-based kojic acid analogues as inhibitors of mushroom tyrosinase

Bioorg Med Chem Lett. 2017 Feb 1;27(3):530-532. doi: 10.1016/j.bmcl.2016.12.027. Epub 2016 Dec 9.

Abstract

Two series of novel kojic acid analogues (4a-j) and (5a-d) were designed and synthesized, and their mushroom tyrosinase inhibitory activities was evaluated. The result indicated that all the synthesized derivatives exhibited excellent tyrosinase inhibitory properties having IC50 values in the range of 1.35±2.15-17.50±2.75μM, whereas standard inhibitor kojic acid have IC50 values 20.00±1.08μM. Specifically, 5-phenyl-3-[5-hydroxy-4-pyrone-2-yl-methylmercap-to]-4-(2,4-dihydroxyl-benzylamino)-1,2,4-triazole (4f) exhibited the most potent tyrosinase inhibitory activity with IC50 value of 1.35±2.15μM. The kinetic studies of the compound (4f) demonstrated that the inhibitory effects of the compound on the tyrosinase were belonging to competitive inhibitors. Meanwhile, the structure-activity relationship was discussed.

Keywords: 1,2,4-Triazole; Benzaldehyde; Kojic acid; Tyrosinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / enzymology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Pyrones / chemical synthesis
  • Pyrones / chemistry
  • Pyrones / pharmacology*
  • Structure-Activity Relationship
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • 5-phenyl-3-(5-hydroxy-4-pyrone-2-yl-methylmercapto)-4-(2,4-dihydroxylbenzylamino)-1,2,4-triazole
  • Enzyme Inhibitors
  • Pyrones
  • Triazoles
  • kojic acid
  • Monophenol Monooxygenase