Antitumor agents. 250. Design and synthesis of new curcumin analogues as potential anti-prostate cancer agents

被引：157

作者：

Lin, Li

Shi, Qian

Nyarko, Alexander K.

Bastow, Kenneth F.

Wu, Chin-Chung

Su, Ching-Yuan

Shih, Charles C. -Y.

Lee, Kuo-Hsiung ^{[1
]}

机构：

[1] Univ N Carolina, Sch Pharm, Nat Prod Lab, Chapel Hill, NC 27599 USA

[2] Androsci Corp, San Diego, CA 92121 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 13期

关键词：

D O I：

10.1021/jm051043z

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In a continuing study of curcumin analogues as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogues classified into four series: monophenyl analogues ( series A), heterocycle-containing analogues ( series B), analogues bearing various substituents on the phenyl rings ( series C), and analogues with various linkers ( series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells, seven only against LNCaP, and one solely against PC-3. This study established an advanced structure-activity relationship ( SAR), and these correlations will guide the further design of new curcumin analogues with better anti-prostate cancer activity.

引用

页码：3963 / 3972

页数：10

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