γ-Lactone-functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I

被引：30

作者：

Tormo, JR

Estornell, E

Gallardo, T

González, MC

Cavé, A

Granell, S

Cortes, D ^{[1
]}

Zafra-Polo, MC

机构：

[1] Univ Valencia, Dept Farmacol Farmacognosia & Farmacodinam, E-46100 Burjassot, Valencia, Spain

[2] Univ Valencia, Fac Farm, Dept Bioquim & Biol Mol, E-46100 Burjassot, Valencia, Spain

[3] Fac Pharm Montpellier, Ctr Biochim Struct, F-34060 Montpellier 1, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 05期

关键词：

D O I：

10.1016/S0960-894X(01)00036-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To study the relevance of the terminal alpha,beta -unsaturated gamma -methyl-gamma -lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta -hydroxy gamma -methyl gamma -lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

页码：681 / 684

页数：4

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