Discovery of a new potent inhibitor of mushroom tyrosinase (Agaricus bisporus) containing 4-(4-hydroxyphenyl)piperazin-1-yl moiety

Bioorg Med Chem. 2020 Jun 1;28(11):115497. doi: 10.1016/j.bmc.2020.115497. Epub 2020 Apr 12.

Abstract

Tyrosinase (TYR, EC 1.14.18.1) plays a pivotal role in mammalian melanogenesis and enzymatic browning of plant-derived food. Therefore, tyrosinase inhibitors (TYRIs) can be of interest in cosmetics and pharmaceutical industries as depigmentation compounds as well as anti-browning agents. Starting from 4-benzylpiperidine derivatives that showed good inhibitory properties toward tyrosinase from Agaricus bisporus (TyM), we synthesized a new series of TYRIs named 3-(4-benzyl-1-piperidyl)-1-(4-phenylpiperazin-1-yl)propan-1-one and 2-(4-benzyl-1-piperidyl)-1-(4-phenylpiperazin-1-yl)ethanone derivatives. Among them, compound 4b proved to be the most potent inhibitor (IC50 = 3.80 µM) and it also showed a good antioxidant activity. These new data furnished additional information about the SAR for this class of TYRIs.

Keywords: Agaricus Bisporus; Docking studies; Hela cells; Phenylpiperazines; Tyrosinase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agaricales / enzymology*
  • Antioxidants / chemical synthesis
  • Antioxidants / chemistry
  • Antioxidants / pharmacology*
  • Cell Survival
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • HeLa Cells
  • Humans
  • Molecular Structure
  • Monophenol Monooxygenase / antagonists & inhibitors*
  • Monophenol Monooxygenase / metabolism
  • Piperazine / chemical synthesis
  • Piperazine / chemistry
  • Piperazine / pharmacology*
  • Structure-Activity Relationship
  • Sulfonic Acids / antagonists & inhibitors
  • Thiazoles / antagonists & inhibitors

Substances

  • 2,2-azinobis-3-ethylbenxothiazoline-6-sulfonic acid
  • Antioxidants
  • Enzyme Inhibitors
  • Sulfonic Acids
  • Thiazoles
  • Piperazine
  • Monophenol Monooxygenase