Madurahydroxylactone derivatives as dual inhibitors of human immunodeficiency virus type 1 integrase and RNase H

被引：37

作者：

Marchand, Christophe ^{[1
]}

Beutler, John A. ^{[2
]}

Wamiru, Antony ^{[2
,3
]}

Budihas, Scott ^{[4
]}

Moellmann, Ute ^{[5
]}

Heinisch, Lothar ^{[6
]}

Mellors, John W. ^{[7
]}

Le Grice, Stuart F. ^{[4
]}

Pommier, Yves ^{[1
]}

机构：

[1] NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA

[2] NCI, Canc Res Ctr, Mol Targets Dev Program, Frederick, MD USA

[3] SAIC, Frederick, MD USA

[4] NCI, Canc Res Ctr, HIV Drug Resistance Program, Frederick, MD USA

[5] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Mol & Appl Microbiol, Jena, Germany

[6] Hans Knoell Inst, Leibniz Inst Nat Prod Res & Infect Biol, Dept Biomol Chem, Jena, Germany

[7] Univ Pittsburgh, Med Ctr, Div Infect Dis, Pittsburgh, PA USA

来源：

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY | 2008年 / 52卷 / 01期

关键词：

D O I：

10.1128/AAC.00883-07

中图分类号：

Q93 [微生物学];

学科分类号：

071005 ; 100705 ;

摘要：

A series of 29 madurahydroxylactone derivatives was evaluated for dual inhibition of human immunodeficiency virus type 1 (HIV-1) integrase and RNase H. While most of the compounds exhibited similar potencies for both enzymes, two of the derivatives showed 10- to 100-fold-higher selectivity for each enzyme, suggesting that distinct pharmacophore models could be generated. This study exemplifies the common and divergent structural requirements for the inhibition of two structurally related HIV-1 enzymes and demonstrates the importance of systematically screening for both integrase and RNase H when developing novel inhibitors.

引用

页码：361 / 364

页数：4

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