First Structure-Activity Relationship Study of Potent BLT2 Agonists as Potential Wound-Healing Promoters

J Med Chem. 2020 Oct 22;63(20):11548-11572. doi: 10.1021/acs.jmedchem.0c00588. Epub 2020 Oct 6.

Abstract

The first potent leukotriene B4 (LTB4) receptor type 2 (BLT2) agonists, endogenous 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT), and synthetic CAY10583 (CAY) have been recently described to accelerate wound healing by enhanced keratinocyte migration and indirect stimulation of fibroblast activity in diabetic rats. CAY represents a very valuable starting point for the development of novel wound-healing promoters. In this work, the first structure-activity relationship study for CAY scaffold-based BLT2 agonists is presented. The newly prepared derivatives showed promising in vitro wound-healing activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Survival / drug effects
  • Cricetulus
  • Drug Development / methods*
  • HaCaT Cells
  • Hep G2 Cells
  • Humans
  • Keratinocytes / drug effects*
  • Keratinocytes / metabolism
  • Molecular Structure
  • Receptors, Leukotriene B4 / agonists*
  • Receptors, Leukotriene B4 / genetics
  • Structure-Activity Relationship
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • LTB4R2 protein, human
  • Receptors, Leukotriene B4