Wound healing effects of new 15-hydroxyprostaglandin dehydrogenase inhibitors

Prostaglandins Leukot Essent Fatty Acids. 2014 Dec;91(6):325-32. doi: 10.1016/j.plefa.2014.09.011.

Abstract

Previously, we reported that the antidiabetic drug ciglitazone and its analogs were potent inhibitors of 15-hydroxyprostaglandin dehydrogenase (15-PGDH). In continuing attempts to develop highly potent 15-PGDH inhibitors, a series of thiazolidinedione analogs were synthesized and tested. Compound 17 exhibited IC50 of 45 nM. This compound also significantly increased levels of prostaglandin E2 (PGE2) in A549 cells by approximately eight-fold that in the control. Much experimental data suggests that PGE2 plays a role in the prevention of excessive scarring. However, it has a very short half-life in blood, its oxidization to 15-ketoprostaglandins is catalyzed by 15-PGDH. Therefore, 15-PGDH inhibitors may have utility for the therapeutic management of diseases requiring elevated PGE2 levels. Scratch wounds were analyzed in confluent monolayers of HaCaT cells. Cells exposed to compound 17 showed significantly improved wound healing with respect to a control.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Bronchiolo-Alveolar
  • Animals
  • Benzylidene Compounds / chemical synthesis
  • Benzylidene Compounds / pharmacology*
  • Cell Line
  • Cell Line, Tumor
  • Cicatrix / prevention & control
  • Dinoprostone / analysis
  • Dinoprostone / blood
  • Dinoprostone / physiology
  • Enzyme Inhibitors / pharmacology*
  • Guinea Pigs
  • Half-Life
  • Humans
  • Hydroxyprostaglandin Dehydrogenases / antagonists & inhibitors*
  • Male
  • Skin / injuries
  • Thiazolidinediones / chemical synthesis
  • Thiazolidinediones / pharmacology*
  • Wound Healing / drug effects*

Substances

  • 5-(2-chloro-3-(3-phenylpropoxy)benzylidene)thiazolidine-2,4-dione
  • Benzylidene Compounds
  • Enzyme Inhibitors
  • Thiazolidinediones
  • Hydroxyprostaglandin Dehydrogenases
  • 15-hydroxyprostaglandin dehydrogenase
  • Dinoprostone