Polyyne hybrid compounds from Notopterygium incisum with peroxisome proliferator-activated receptor gamma agonistic effects

J Nat Prod. 2014 Nov 26;77(11):2513-21. doi: 10.1021/np500605v. Epub 2014 Oct 21.

Abstract

In the search for peroxisome proliferator-activated receptor gamma (PPARγ) active constituents from the roots and rhizomes of Notopterygium incisum, 11 new polyacetylene derivatives (1-11) were isolated. Their structures were elucidated by NMR and HRESIMS as new polyyne hybrid molecules of falcarindiol with sesquiterpenoid or phenylpropanoid moieties, named notoethers A-H (1-8) and notoincisols A-C (9-11), respectively. Notoincisol B (10) and notoincisol C (11) represent two new carbon skeletons. When tested for PPARγ activation in a luciferase reporter assay with HEK-293 cells, notoethers A-C (1-3), notoincisol A (9), and notoincisol B (10) showed promising agonistic activity (EC50 values of 1.7 to 2.3 μM). In addition, notoincisol A (9) exhibited inhibitory activity on NO production of stimulated RAW 264.7 macrophages.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apiaceae / chemistry*
  • Diynes / pharmacology
  • Fatty Alcohols / pharmacology
  • HEK293 Cells
  • Humans
  • Lipopolysaccharides / pharmacology
  • Luciferases / metabolism
  • Macrophages / drug effects
  • Mice
  • Molecular Structure
  • Nitric Oxide / biosynthesis
  • PPAR gamma / drug effects*
  • Plant Roots / chemistry
  • Polyynes / chemistry
  • Polyynes / isolation & purification*
  • Polyynes / pharmacology*
  • Rhizome / chemistry

Substances

  • Diynes
  • Fatty Alcohols
  • Lipopolysaccharides
  • PPAR gamma
  • notoincisol B
  • Polyynes
  • Nitric Oxide
  • falcarindiol
  • Luciferases