Synthesis and Biological Evaluation of Dimeric Furanoid Macroheterocycles: Discovery of New Anticancer Agents

被引：7

作者：

Nicolaou, K. C. ^{[1
]}

Nilewski, Christian ^{[1
]}

Hale, Christopher R. H. ^{[1
]}

Ahles, Christopher F. ^{[3
]}

Chiu, Chiao An ^{[3
]}

Ebner, Christian ^{[3
]}

ElMarrouni, Abdelatif ^{[1
]}

Yang, Lifeng ^{[2
]}

Stiles, Katherine ^{[2
]}

Nagrath, Deepak ^{[2
]}

机构：

[1] Rice Univ, Dept Chem BioSci Res Collaborat, Houston, TX 77005 USA

[2] Rice Univ, Dept Chem & Biomol Engn, Houston, TX 77005 USA

[3] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2015年 / 137卷 / 14期

基金：

美国国家卫生研究院;

关键词：

NATURAL-PRODUCTS; MITOCHONDRIA;

D O I：

10.1021/jacs.5b00141

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A recently developed dimerization/macrocyclization was employed to synthesize a series of macroheterocycles which were biologically evaluated, leading to the discovery of a number of potent cytotoxic agents (e.g., 27: GI(50) = 51 nM against leukemia CCRF-CEM cell line; 29: GI(50) = 99 nM against melanoma MDA-MB-435 cell line). Further biological studies support an apoptosis mechanism of action for these compounds involving deregulation of the tricarboxylic acid cycle activity and suppression of mitochondrial function in cancer cells.

引用

页码：4766 / 4770

页数：5

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