Cytotoxic Flavonoids as Agonists of Peroxisome Proliferator-Activated Receptor γ on Human Cervical and Prostate Cancer Cells
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- 作者：Jee-Young Lee ; Jin-Kyoung Kim ; Min-Chul Cho ; Soyoung Shin ; Do-Young Yoon ; Yong Seok Heo ; Yangmee Kim
- 刊名：Journal of Natural Products
- 出版年：2010
- 出版时间：July 23, 2010
- 年：2010
- 卷：73
- 期：7
- 页码：1261-1265
- 全文大小：269K
- 年卷期：v.73,no.7(July 23, 2010)
- ISSN：1520-6025
文摘
We conducted in silico screening for human peroxisome proliferator-activated receptor gamma (hPPARγ) by performing an automated docking study with 450 flavonoids. Among the eight flavonoids as possible agonists of hPPARγ, only 3,6-dihydroxyflavone (4) increased the binding between PPARγ and steroid receptor coactivator-1 (SRC-1), approximately 5-fold, and showed one order higher binding affinity for PPARγ than a reference compound, indomethacin. The 6-hydroxy group of 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 agonist of hPPAR with cytotoxic effects on human cervical and prostate cancer cells.