Synthesis and antimalarial activity of new chloroquine analogues carrying a multifunctional linear side chain

被引：38

作者：

Iwaniuk, Daniel P. ^{[1
]}

Whetmore, Eric D. ^{[1
]}

Rosa, Nicholas ^{[1
]}

Ekoue-Kovi, Kekeli ^{[1
]}

Alumasa, John ^{[1
]}

de Dios, Angel C. ^{[1
,3
]}

Roepe, Paul D. ^{[1
,2
,3
]}

Wolf, Christian ^{[1
,3
]}

机构：

[1] Georgetown Univ, Dept Chem, Washington, DC 20057 USA

[2] Georgetown Univ, Dept Biochem & Cellular & Mol Biol, Washington, DC 20057 USA

[3] Georgetown Univ, Ctr Infect Dis, Washington, DC 20057 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2009年 / 17卷 / 18期

基金：

美国国家科学基金会; 美国国家卫生研究院;

关键词：

Chloroquine; Malaria; 4-Aminoquinolines; 4-Alkoxyquinolines; Resistance index; PIGMENT BETA-HEMATIN; PLASMODIUM-FALCIPARUM; MALARIA PARASITES; DRUG-RESISTANCE; RETAIN ACTIVITY; INHIBITION; COMPLEX; GROWTH; 4-AMINOQUINOLINES; AMINOQUINOLINES;

D O I：

10.1016/j.bmc.2009.08.003

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report the synthesis and in vitro antimalarial activity of several new 4-amino- and 4-alkoxy-7-chloroquinolines carrying a linear dibasic side chain. Many of these chloroquine analogues have submicromolar antimalarial activity versus HB3 (chloroquine sensitive) and Dd2 (chloroquine resistant strain of Plasmodium falciparum) and low resistance indices were obtained in most cases. Importantly, compounds 11-15 and 24 proved to be more potent against Dd2 than chloroquine. Branching of the side chain structure proved detrimental to the activity against the CQR strain. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：6560 / 6566

页数：7

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