4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle.
4-Nitro styrylquinoline is an antimalarial inhibiting multiple stages of Plasmodium falciparum asexual life cycle.
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DOI：
10.1016/j.ijpddr.2017.02.002
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发表时间：
2017-04
期刊：
影响因子：
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通讯作者：
Chakrabarti D
中科院分区：
文献类型：
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作者：
Roberts BF;Zheng Y;Cleaveleand J;Lee S;Lee E;Ayong L;Yuan Y;Chakrabarti D
由于出现抗药性，防治疟疾的药物正在失去效力。这突出表明需要具有不同于当前抗疟药的作用机制的新型疟疾治疗选择。为了鉴定抗疟疾的新型药效团，我们筛选了含有与疟疾相关的天然产物的结构特征的化合物。该筛选确定了具有亚微摩尔抗疟原虫活性和优异选择性的4-硝基苯乙烯基喹啉（SQ）化合物。SQ表现出与当前抗疟药不同的细胞作用，在疟原虫的红细胞内生命周期早期起作用，包括裂殖子侵入。该化合物是一种快速作用的杀寄生虫剂，并且当口服给药时，在啮齿动物疟疾模型中也表现出治疗性质。在这份报告中，我们描述了合成，初步的结构-功能分析，和寄生虫发育阶段的具体行动的SQ支架。
Drugs against malaria are losing their effectiveness because of emerging drug resistance. This underscores the need for novel therapeutic options for malaria with mechanism of actions distinct from current antimalarials. To identify novel pharmacophores against malaria we have screened compounds containing structural features of natural products that are pharmacologically relevant. This screening has identified a 4-nitro styrylquinoline (SQ) compound with submicromolar antiplasmodial activity and excellent selectivity. SQ exhibits a cellular action distinct from current antimalarials, acting early on malaria parasite's intraerythrocytic life cycle including merozoite invasion. The compound is a fast-acting parasitocidal agent and also exhibits curative property in the rodent malaria model when administered orally. In this report, we describe the synthesis, preliminary structure-function analysis, and the parasite developmental stage specific action of the SQ scaffold.