In vitro antiplasmodial activity of triazole-linked chloroquinoline derivatives synthesized from 7-chloro-N-(prop-2-yn-1-yl)quinolin-4-amine

被引：18

作者：

Taleli, Lebusetsa ^{[1
]}

de Kock, Carmen ^{[2
]}

Smith, Peter J. ^{[2
]}

Pelly, Stephen C. ^{[1
]}

Blackie, Margaret A. L. ^{[1
]}

van Otterlo, Willem A. L. ^{[1
]}

机构：

[1] Univ Stellenbosch, Dept Chem & Polymer Sci, ZA-7602 Matieland, South Africa

[2] Univ Cape Town, Dept Med, Div Pharmacol, ZA-7925 Observatory, South Africa

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2015年 / 23卷 / 15期

基金：

新加坡国家研究基金会;

关键词：

Antiplasmodial; 4-Aminoquinoline; CuAAC click chemistry; Triazole linkers; Resistance reversal; PLASMODIUM-FALCIPARUM; BIOLOGICAL EVALUATION; ANTIMALARIAL ACTIVITY; HYBRID MOLECULES; CLICK CHEMISTRY; RETAIN ACTIVITY; ANALOGS; RESISTANCE; DESIGN; SERIES;

D O I：

10.1016/j.bmc.2015.06.044

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：

The synthesis and in vitro evaluation of novel triazole-linked chloroquinoline derivatives as potential antiplasmodial agents against Plasmodium falciparum is reported. The 15 synthesized target compounds were obtained by means of a copper(I)-mediated click reaction between a variety of 1,2- and 1,3-azidoamines and 7-chloro-N-(prop-2-yn-1-yl) quinolin-4-amine in moderate to good yields (53-85%). The compounds were screened for antiplasmodial activity against NF54 chloroquine-sensitive and Dd2 chloroquine-resistant strains, alongside chloroquine and artesunate as reference compounds. Six of the test compounds revealed a 3-5 fold increase in antiplasmodial activity against chloroquine-resistant strain Dd2 compared to chloroquine. Among the six compounds with good antiplasmodial activity, a reduced cross-resistance relative to artesunate (>3 fold in comparison to chloroquine) was observed, mainly in derivatives that incorporated chloroquine-resistance reversing pharmacophores. A general trend for reduced chloroquine cross-resistance was also detected among 12 out of the 15 compounds tested. (C) 2015 Elsevier Ltd. All rights reserved.

引用

页码：4163 / 4171

页数：9

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