Synthesis and structure-activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents

被引：59
|
作者：
Vicente, Esther [1 ,2 ]
Lima, Lidia M. [1 ]
Bongard, Emily [2 ]
Charnaud, Sarah [2 ]
Villar, Raquel [1 ]
Solano, Beatriz [1 ]
Burguete, Asuncion [1 ]
Perez-Silanes, Silvia [1 ]
Aldana, Ignacio [1 ]
Vivas, Livia [2 ]
Monge, Antonio [1 ]
机构：
[1] Univ Navarra, Unidad Invest & Desarrollo Medicamentos, CIFA, E-31080 Pamplona, Spain
[2] Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1E 7HT, England
来源：
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2008年 / 43卷 / 09期
关键词：
Quinoxaline; N-Oxide; Beirut reaction; Antiplasmodial; Malaria; Plasmodium falciparum;
D O I：
10.1016/j.ejmech.2007.11.024
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
As a continuation of our research and with the aim of obtaining new antimalarial agents, new series of 3-phenylquinoxaline 1,4-di-N-oxide derivatives have been synthesized following the classical Beirut reaction. Antiplasmodial activity was evaluated in vitro against Plasmodium falciparum by the incorporation of [H-3]-hypoxanthine. Cytotoxicity was tested in KB cells by AlamarBlue assay. Twenty-one of the 60 compounds that were assayed against 3D7 (CQ-sensitive) showed enough activity to be also evaluated against K1 (CQ-resistant) strain. Ten of them were shown to be more active than chloroquine in the resistant strain. The most interesting compounds are 7-(methyl or methoxy)-3-(4'-fluoro or chloro)phenylquinoxaline-2-carbonitrile 1,4-di-N-oxides because of their low IC50 and their high SI shown for the K1 strain, making them valid new leads. (C) 2007 Elsevier Masson SAS. All rights reserved.
引用
收藏
页码：1903 / 1910
页数：8
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