Synthesis and PGE2 inhibitory activity of novel diarylheptanoids

Bioorg Med Chem Lett. 2018 Feb 1;28(3):334-338. doi: 10.1016/j.bmcl.2017.12.046. Epub 2017 Dec 21.

Abstract

Prostaglandin E2 (PGE2) is a lipid mediator of inflammation and its inhibition has become a popular drug target due to its harmful physiological roles. Diarylheptanoids are one class of compounds that have shown successful inhibition of PGE2. This paper reports the synthesis and PGE2 inhibitory activity of a series of analogues of a naturally occurring diarylheptanoid. The most efficacious compounds were examined for dose-dependent PGE2 inhibition. Among several promising compounds, the lead candidate exhibited an IC50 value of 0.56 ng/µL or 1.7 µM with no detectable toxicity at the highest dose of 10 ng/µL.

Keywords: Cross metathesis; Curcumin; Diarylheptanoids; Inflammation; Prostaglandin E(2).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Diarylheptanoids / chemical synthesis
  • Diarylheptanoids / chemistry
  • Diarylheptanoids / pharmacology*
  • Dinoprostone / antagonists & inhibitors*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Diarylheptanoids
  • Dinoprostone