Novel, Broad Spectrum Anticancer Agents Containing the Tricyclic 5:7:5-Fused Diimidazodiazepine Ring System

被引：51

作者：

Kondaskar, Atul ^{[1
]}

Kondaskar, Shilpi ^{[1
]}

Kumar, Raj ^{[1
]}

Fishbein, James C. ^{[1
]}

Muvarak, Nidal ^{[2
,3
]}

Lapidus, Rena G. ^{[2
,3
]}

Sadowska, Mariola ^{[2
,3
]}

Edelman, Martin J. ^{[2
,3
]}

Bol, Guus M. ^{[4
]}

Vesuna, Farhad ^{[4
]}

Raman, Venu ^{[4
]}

Hosmane, Ramachandra S. ^{[1
]}

机构：

[1] Univ Maryland, Dept Chem & Biochem, Lab Drug Design & Synth, Baltimore, MD 21250 USA

[2] Univ Maryland, Translat Core Lab, Baltimore, MD 21201 USA

[3] Stewart Greenbaum Canc Ctr, Baltimore, MD 21201 USA

[4] Johns Hopkins Univ, Dept Radiol, Sch Med, Baltimore, MD 21205 USA

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2011年 / 2卷 / 03期

基金：

美国国家卫生研究院;

关键词：

Synthesis; 5:7:5-fused tricycles; diimidazo[4,5-d:4 ',5 '- f][1,3]diazepine ring system; in vitro screening; broad spectrum anticancer activity; prostate; lung; breast; and ovarian cancers; preliminary mechanistic studies; effects on G1 and S phases of the cell cycle; P68 RNA HELICASE; CELL-PROLIFERATION; CANCER; EXPRESSION; ANALOGS; GENE;

D O I：

10.1021/ml100281b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis of a series of novel, broad spectrum anticancer agents containing the tricyclic 5:7:5-fused diimidazo[4,5-d:4',5'-f][1,3]diazepine ring system is reported. Compounds 1, 2, 8, 11, and 12 in the series show promising in vitro antitumor activity with low micromolar IC50 values against prostate, lung, breast, and ovarian cance:r cell lines. Some notions about structure-activity relationships and a possible mechanism of biological activity are presented. Also presented are preliminary in vivo toxicity studies of 1 using SCID mice.

引用

页码：252 / 256

页数：5

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