Doxazosin-Related α1-Adrenoceptor Antagonists With Prostate Antitumor Activity

被引：36

作者：

Giardina, Dario ^{[1
]}

Martarelli, Daniele ^{[2
]}

Sagratini, Gianni ^{[1
]}

Angeli, Piero ^{[1
]}

Ballinari, Dario ^{[3
]}

Gulini, Ugo ^{[1
]}

Melchiorre, Carlo ^{[5
]}

Poggesi, Elena ^{[4
]}

Pompei, Pierluigi ^{[2
]}

机构：

[1] Univ Camerino, Dept Chem Sci, I-62032 Camerino, Italy

[2] Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, Italy

[3] Nerviano Med Sci, Dept Oncol, Nerviano, MI, Italy

[4] Recordati SpA, Pharmaceut R&D Div, Milan, Italy

[5] Univ Bologna, Dept Pharmaceut Sci, I-40126 Bologna, Italy

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2009年 / 52卷 / 15期

关键词：

DERIVATIVES; APOPTOSIS; CANCER; HYPERPLASIA; TERAZOSIN; EFFICACY; BLOCKADE; SUBTYPE;

D O I：

10.1021/jm8016046

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Doxazosin analogues 1-3 and 1 a were synthesized and investigated at alpha(1)-adrenoceptors and PC-3, DU-145, and LNCaP human prostate cancer cells. Compound 1 (cyclodoxazosin) was a potent alpha(1B)-adrenoceptor antagonist displaying anti proliferative activity higher than that of doxazosin in cancer cells in vitro and in vivo, respectively. Because of its antitumor efficacy at low concentrations, lower apoptotic activity in NHDF vs tumor cells, and antiangiogenetic effect, 1 showed a better therapeutic profile relative to doxazosin.

引用

页码：4951 / 4954

页数：4

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