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.
| Original language | English |
|---|---|
| Journal | Journal of Natural Products |
| Volume | 75 |
| Issue number | 7 |
| Pages (from-to) | 1332-8 |
| Number of pages | 7 |
| ISSN | 0163-3864 |
| DOIs | |
| Publication status | Published - 27 Jul 2012 |
Keywords
- Ailanthus
- Amino Acid Sequence
- Coumarins
- Humans
- Luciferases
- Molecular Structure
- NAD
- Nuclear Magnetic Resonance, Biomolecular
- Plant Bark
- Plant Stems
- Republic of Korea
- Sirtuin 1
- Stereoisomerism
- Journal Article
- Research Support, Non-U.S. Gov't