Synthesis and biological evaluation of novel flavonols as potential anti-prostate cancer agents

被引：37

作者：

Britton, Robert G. ^{[2
]}

Horner-Glister, Emma ^{[1
]}

Pomenya, Odette A. ^{[1
]}

Smith, Ewan E. ^{[3
]}

Denton, Roanne ^{[3
]}

Jenkins, Paul R. ^{[3
]}

Steward, William P. ^{[1
]}

Brown, Karen ^{[1
]}

Gescher, Andreas ^{[1
]}

Sale, Stewart ^{[1
]}

机构：

[1] Univ Leicester, Leicester Royal Infirm, RKCSB, Dept Canc Studies & Mol Med, Leicester LE2 7LX, Leics, England

[2] Univ Leicester, Dept Canc Studies & Mol Med, Leicester LE1 7RH, Leics, England

[3] Univ Leicester, Dept Chem, Leicester LE1 7RH, Leics, England

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2012年 / 54卷

关键词：

Flavonols; AR signalling pathway; Prostate cancer management; CELL-CYCLE ARREST; ANDROGEN RECEPTOR; QUERCETIN; APOPTOSIS; EXPRESSION; EFFICACY; FISETIN; LINES;

D O I：

10.1016/j.ejmech.2012.06.031

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A library of flavonol analogues was synthesised and evaluated as potential anticancer agents against a human prostate cancer cell line, 22rv1. Compounds 3, 8 and 11 (IC50 2.6, 3.3 and 4.0 mu M respectively) showed potent cancer cell growth inhibition, comparable to the lead compound 3',4',5'-trimethoxyflavonol (1) (IC50 3.1 mu M) and superior to the naturally occurring flavonols quercetin (16) and fisetin (22) (both >15 mu M). Results indicate that the 3',4',5'- arrangement of either hydroxy (OH) or methoxy (OMe) residues is important for growth arrest of these cells and that the OMe analogues may be superior to their OH counterparts. Compounds 1, 3, 8 and 11 warrant further investigation as potential agents for the management of prostate cancer. (C) 2012 Elsevier Masson SAS. All rights reserved.

引用

页码：952 / 958

页数：7

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