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

被引：17
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
收藏
页码：1261 / 1265
页数：5
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