Cytotoxic Flavonoids as Agonists of Peroxisome Proliferator-Activated Receptor γ on Human Cervical and Prostate Cancer Cells

被引：16

作者：

Lee, Jee-Young ^{[1
,2
]}

Kim, Jin-Kyoung ^{[1
,2
]}

Cho, Min-Chul ^{[1
,2
]}

Shin, Soyoung ^{[1
,2
]}

Yoon, Do-Young ^{[1
,2
]}

Heo, Yong Seok ^{[3
]}

Kim, Yangmee ^{[1
,2
]}

机构：

[1] Konkuk Univ, Dept Biosci & Biotechnol, Seoul 143701, South Korea

[2] Konkuk Univ, Bio Mol Informat Ctr, Seoul 143701, South Korea

[3] Konkuk Univ, Dept Chem, Seoul 143701, South Korea

来源：

JOURNAL OF NATURAL PRODUCTS | 2010年 / 73卷 / 07期

关键词：

PPAR-GAMMA; NUCLEAR RECEPTORS; FLEXIBLE DOCKING; LIGAND-BINDING; METABOLISM; ALPHA; SELECTIVITY; MINIREVIEW; DISEASE; TARGETS;

D O I：

10.1021/np100148m

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

We conducted in silico screening for human peroxisome proliferator-activated receptor gamma (hPPAR gamma) by performing in automated docking study with 450 flavonoids. Among the eight flavonoids is possible agonises of hPPAR gamma, only 3,6-dihydroxyflavone (4) increased the binding between PPAR gamma and steroid receptor coactivator-I (SRC-I), approximately 5-fold, and showed one order higher binding affinity for PPAR gamma than a reference compound, indomethacin. The 6-hydroxy group or the A-ring of 3,6-dihydroxyflavone (4) participated in hydrogen-bonding interactions with the side chain of Tyr327, His449, and Tyr473. The B-ring formed a hydrophobic interaction with Leu330, Leu333, Val339, Ile341, and Met364. Therefore, 3,6-dihydroxyflavone is a potent agonise of hPPAR with cytotoxic effects on human cervical and prostate cancer cells.

引用

页码：1261 / 1265

页数：5

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