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
收藏
页码：681 / 684
页数：4
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