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 |
|---|---|
| Pages (from-to) | 1332-1338 |
| Number of pages | 7 |
| Journal | Journal of Natural Products |
| Volume | 75 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - 2012 Jul 27 |
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All Science Journal Classification (ASJC) codes
- Analytical Chemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry
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Terpenylated coumarins as SIRT1 activators isolated from ailanthus altissima. / Dao, Trong Tuan; Tran, Tien Lam; Kim, Jayeon; Nguyen, Phi Hung; Lee, Eun Hee; Park, Junsoo; Jang, Ik Soon; Oh, Won Keun.
In: Journal of Natural Products, Vol. 75, No. 7, 27.07.2012, p. 1332-1338.Research output: Contribution to journal › Article
TY - JOUR
T1 - Terpenylated coumarins as SIRT1 activators isolated from ailanthus altissima
AU - Dao, Trong Tuan
AU - Tran, Tien Lam
AU - Kim, Jayeon
AU - Nguyen, Phi Hung
AU - Lee, Eun Hee
AU - Park, Junsoo
AU - Jang, Ik Soon
AU - Oh, Won Keun
PY - 2012/7/27
Y1 - 2012/7/27
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84864186332&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864186332&partnerID=8YFLogxK
U2 - 10.1021/np300258u
DO - 10.1021/np300258u
M3 - Article
C2 - 22799262
AN - SCOPUS:84864186332
VL - 75
SP - 1332
EP - 1338
JO - Journal of Natural Products
JF - Journal of Natural Products
SN - 0163-3864
IS - 7
ER -