Synthesis and anticancer activity of epipolythiodiketopiperazine alkaloids

被引：74

作者：

Boyer, Nicolas ^{[1
]}

Morrison, Karen C. ^{[2
]}

Kim, Justin ^{[1
]}

Hergenrother, Paul J. ^{[2
]}

Movassaghi, Mohammad ^{[1
]}

机构：

[1] MIT, Dept Chem, Cambridge, MA 02139 USA

[2] Univ Illinois, Dept Chem, Urbana, IL 61801 USA

来源：

CHEMICAL SCIENCE | 2013年 / 4卷 / 04期

基金：

美国国家卫生研究院;

关键词：

CONCISE TOTAL-SYNTHESIS; CYTOTOXIC METABOLITES; ANTIBIOTICS GLIOTOXIN; ANTIVIRAL ACTIVITY; LEPTOSPHAERIA SP; GENERAL-APPROACH; FUNGAL TOXIN; CELL-DEATH; CHAETOCIN; SPORIDESMIN;

D O I：

10.1039/c3sc50174d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The epipolythiodiketopiperazine (ETP) alkaloids are a highly complex class of natural products with potent anticancer activity. Herein, we report the application of a flexible and scalable synthesis, allowing the construction of dozens of ETP derivatives. The evaluation of these compounds against cancer cell lines in culture allows for the first expansive structure-activity relationship (SAR) to be defined for monomeric and dimeric ETP-containing natural products and their synthetic cognates. Many ETP derivatives demonstrate potent anticancer activity across a broad range of cancer cell lines and kill cancer cells via induction of apoptosis. Several traits that bode well for the translational potential of the ETP class of natural products include concise and efficient synthetic access, potent induction of apoptotic cell death, activity against a wide range of cancer types, and a broad tolerance for modifications at multiple sites that should facilitate small-molecule drug development, mechanistic studies, and evaluation in vivo.

引用

页码：1646 / 1657

页数：12

共 103 条

[1] A concise approach to the epidithiodiketopiperazine (ETP) core [J].