Terpenylated coumarins as SIRT1 activators isolated from Ailanthus altissima

J Nat Prod. 2012 Jul 27;75(7):1332-8. doi: 10.1021/np300258u. Epub 2012 Jul 16.

Abstract

Four new terpenylated coumarins (1-4) were isolated from the stem bark of Ailanthus altissima by bioactivity-guided fractionation using an in vitro SIRT1 deacetylation assay. Their structures were identified as (2'R,3'R)-7-(2',3'-dihydroxy-3',7'-dimethylocta-6'-enyloxy)-6,8-dimethoxycoumarin (1), 6,8-dimethoxy-7-(3',7'-dimethylocta-2',6'-dienyloxy)coumarin (2), (2'R,3'R,6'R)-7-(2',3'-dihydroxy-6',7'-epoxy-3',7'-dimethyloctaoxy)-6,8-dimethoxycoumarin (3), and (2'R,3'R,4'S,5'S)-6,8-dimethoxy-7-(3',7'-dimethyl-4',5'-epoxy-2'-hydroxyocta-6'-enyloxy)coumarin (4). Compounds 1-4 strongly enhanced SIRT1 activity in an in vitro SIRT1-NAD/NADH assay and an in vivo SIRT1-p53 luciferase assay. These compounds also increased the NAD-to-NADH ratio in HEK293 cells. The present results suggest that terpenylated coumarins from A. altissima have a direct stimulatory effect on SIRT1 deacetylation activity and may serve as lead molecules for the treatment of some age-related disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ailanthus / chemistry*
  • Amino Acid Sequence
  • Coumarins / chemistry
  • Coumarins / isolation & purification*
  • Humans
  • Luciferases / drug effects
  • Luciferases / metabolism
  • Molecular Structure
  • NAD / analysis
  • NAD / metabolism
  • Nuclear Magnetic Resonance, Biomolecular
  • Plant Bark / chemistry
  • Plant Stems / chemistry
  • Republic of Korea
  • Sirtuin 1 / drug effects*
  • Stereoisomerism

Substances

  • Coumarins
  • NAD
  • Luciferases
  • Sirtuin 1