Synthesis and structure-activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents
Synthesis and structure-activity relationship of 3-phenylquinoxaline 1,4-di-N-oxide derivatives as antimalarial agents
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DOI：
10.1016/j.ejmech.2007.11.024
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发表时间：
2008-09-01
影响因子：
6.7
通讯作者：
Monge, Antonio
中科院分区：
文献类型：
--
作者：
Vicente, Esther;Lima, Lidia M.;Monge, Antonio
作为我们研究的延续，以获得新的抗疟药物为目的，根据经典的贝鲁特反应合成了一系列新的3-苯基喹啉1,4-二n -氧化物衍生物。用[H-3]-次黄嘌呤联合体外抗恶性疟原虫活性评价。用AlamarBlue法检测KB细胞的细胞毒性。60个化合物中有21个对3D7 （cq敏感）有足够的活性，也可以对K1 （cq抗性）菌株进行评估。其中10种在耐药菌株中比氯喹更有活性。最有趣的化合物是7-（甲基或甲氧基）-3-（4'-氟或氯）苯基喹啉-2-碳腈1,4-二氮氧化物，因为它们在K1菌株中显示出低IC50和高SI，使它们成为有效的新引线。(C) 2007 Elsevier Masson SAS。版权所有。
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.