Evaluation of Novel Chalcone Oximes as Inhibitors of Tyrosinase and Melanin Formation in B16 Cells

Arch Pharm (Weinheim). 2016 Jan;349(1):20-9. doi: 10.1002/ardp.201500298. Epub 2015 Nov 17.

Abstract

A series of hydroxy-substituted chalcone oxime derivatives were synthesized. These compounds were then evaluated for their inhibitory activities on tyrosinase and melanogenesis in murine B16F10 melanoma cells. The structures of the synthesized compounds were confirmed by (1) H NMR, (13) C NMR, FTIR, and HRMS. Two of the compounds exhibited much higher tyrosinase inhibitory activities (IC50 values of 4.77 and 7.89 μM, respectively) than the positive control, kojic acid (IC50 : 22.25 μM). Kinetic studies revealed them to act as competitive tyrosinase inhibitors with their Ki values of 5.25 and 8.33 μM, respectively. Both the compounds inhibited melanin production and tyrosinase activity in B16 cells. Docking results confirmed that the active inhibitors strongly interacted with the mushroom tyrosinase residues.

Keywords: Chalcone oxime; Competitive; Docking; Tyrosinase inhibition.

MeSH terms

  • Agaricus / enzymology
  • Animals
  • Cell Survival / drug effects
  • Chalcones / chemical synthesis
  • Chalcones / chemistry*
  • Chalcones / pharmacology
  • Melanins / antagonists & inhibitors*
  • Melanins / biosynthesis
  • Melanoma, Experimental
  • Mice
  • Molecular Docking Simulation
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Oximes / chemical synthesis
  • Oximes / chemistry*
  • Oximes / pharmacology
  • Phenols / chemical synthesis
  • Phenols / chemistry*
  • Phenols / pharmacology
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 2-(3-(4-(dimethylamino)phenyl)-N-hydroxyprop-2-enimidoyl)phenol
  • 2-(N-hydroxy-3-(2-methoxy-4-nitrophenyl)prop-2-enimidoyl)phenol
  • Chalcones
  • Melanins
  • Oximes
  • Phenols
  • Monophenol Monooxygenase