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

页码：1903 / 1910

页数：8

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