Natural product-based design, synthesis and biological evaluation of 2',3,4,4'-tetrahydrochalcone analogues as antivitiligo agents

Bioorg Chem. 2019 Jun:87:523-533. doi: 10.1016/j.bioorg.2019.03.054. Epub 2019 Mar 23.

Abstract

A bioactive component, 2',3,4,4'-tetrahydrochalcone (RY3-a) was first isolated from Vernohia anthelmintica (L.) willd seeds, and a set of its analogs, RY3-a-1-RY3-a-15 and RY3-c were designed and synthesized. Biological activity assays showed that RY3-c exhibited better melanogenesis and antioxidant activity and lower toxicity in comparison with RY3-a and butin. Further study tests showed that RY3-c exhibited better melanogenesis activity compared with the positive control 8-methoxypsoralan (8-MOP) in a vitiligo mouse model, suggesting that RY3-c is a good candidate antivitiligo agent. Mechanistic studies showed that RY3-c could repair cell damage induced by excessive oxidative stress and may exert melanin synthesis activity in the mouse melanoma B16F10 cell line by activating the mitogen-activated protein kinase (MAPK) pathway and the upregulation of c-kit.

Keywords: 2′,3,4,4′-Tetrahydrochalcone; C-kit; MAPK; Oxidative stress; Vitiligo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biological Products / chemistry
  • Biological Products / isolation & purification
  • Biological Products / pharmacology*
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Chalcone / analogs & derivatives
  • Chalcone / chemistry
  • Chalcone / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Design*
  • MAP Kinase Signaling System / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • Oxidative Stress / drug effects
  • Structure-Activity Relationship
  • Vernonia / chemistry*
  • Vitiligo / drug therapy*
  • Vitiligo / metabolism
  • Vitiligo / pathology
  • Zebrafish

Substances

  • Biological Products
  • Chalcone