Integrated kinetic studies and computational analysis on naphthyl chalcones as mushroom tyrosinase inhibitors

Bioorg Med Chem Lett. 2015 Oct 1;25(19):4085-91. doi: 10.1016/j.bmcl.2015.08.033. Epub 2015 Aug 18.

Abstract

Melanin helps to protect skin from the damaging ultraviolet radiation of the sun. Tyrosinase, the key enzyme in melanogenesis is responsible for coloration of skin, hair and eyes. This enzyme is considered to have a critical role in governing the quality and economics of fruits and vegetables, as tyrosinase activity can lead to spoilage through browning. Development of tyrosinase inhibitors is a promising approach to combat hyperpigmentation conditions like ephelides, lentigo, freckles and post-inflammatory hyperpigmentation. In the present study, we have used a docking algorithm to simulate binding between tyrosinase and hydroxy-substituted naphthyl chalcone oxime compounds and studied the inhibition of tyrosinase. The results of virtual screening studies indicated that the estimated free energy of binding of all the docked ligands ranged between -19.29 and -9.12 kcal/mol. Two of the oximes synthesized were identified as competitive tyrosinase inhibitors and were found to be twice as potent as the control kojic acid with their IC50 values of 12.22 μM and 19.45 μM, respectively. This strategy of integrating experimental and virtual screening methods could give better insights to explore potent depigmentation agents.

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

MeSH terms

  • Agaricus / enzymology*
  • Algorithms
  • Chalcones / chemical synthesis
  • Chalcones / chemistry*
  • Chalcones / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Kinetics
  • Molecular Docking Simulation*
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / isolation & purification
  • Monophenol Monooxygenase / metabolism
  • Structure-Activity Relationship

Substances

  • Chalcones
  • Enzyme Inhibitors
  • Monophenol Monooxygenase