E-ring-modified 7-oxyiminomethyl camptothecins: Synthesis and preliminary in vitro and in vivo biological evaluation

被引：10

作者：

Giannini, Giuseppe ^{[1
]}

Marzi, Mauro ^{[1
]}

Cabri, Walter ^{[1
]}

Marastoni, Elena ^{[1
]}

Battistuzzi, Gianfranco ^{[1
]}

Vesci, Loredana ^{[1
]}

Pisano, Claudio ^{[1
]}

Beretta, Giovanni Luca ^{[2
]}

De Cesare, Michelandrea ^{[2
]}

Zunino, Franco ^{[2
]}

机构：

[1] Sigma Tau Res & Dev, I-00040 Rome, Italy

[2] Ist Nazl Studio & Cura Tumori, Fondaz IRCCS, I-20133 Milan, Italy

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 09期

关键词：

topoisomerase I inhibitors; homocamptothecins; antitumor;

D O I：

10.1016/j.bmcl.2008.03.074

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

In contrast to five-membered E-ring analogues, 7-oxyiminomethyl derivatives of homocamptothecins showed ability to form stable ternary complexes with DNA and topoisomerase I. The 7-oxyiminomethyl derivatives of homocamptothecins were evaluated as a racemic mixture. Following the isolation of the two enantiomers, the 20 (R)-hydroxy isomer confirms the best activity. By using a panel of human tumor cells, all tested homocamptothecins showed a potent antiproliferative activity, correlating to the persistence of the cleavable complex. No significant difference was observed between the natural scaffold and the corresponding homocamptothecin homologue. A selected compound of this series exhibited an excellent antitumor activity against human gastrointestinal tumor xenografts. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：2910 / 2915

页数：6

共 12 条

[1] Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs [J].