Antimalarial activity of novel arylene bis(methylketone) compounds.
Antimalarial activity of novel arylene bis(methylketone) compounds.
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新型亚芳基双（甲基酮）化合物的抗疟活性。
DOI：
10.1093/infdis/174.3.659
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Ulrich,P
中科院分区：
文献类型：
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作者：
Berger,BJ;Paciorkowski,A;Suskin,M;Dai,WW;Cerami,A;Ulrich,P
由于抗药性疟原虫的传播，迫切需要新型有效的抗疟药物。对一系列亚芳基双（甲基酮）化合物进行了体外抗恶性疟原虫和体内抗伯氏疟原虫的筛选。2-氨基-4-（3，5-二乙酰基苯基）氨基-1，6-二甲基嘧啶鎓氯化物（Cytokine Network Inc. [CNI]-H 0294）是体外最有效的化合物，对氯喹和乙胺嘧啶敏感范围广泛的寄生虫克隆的IC 50为1.5-4.0 µ/M。该系列中的其他化合物的体外IC 50值为20-25 µ/M。在为期4天的抑制P.在体内，50 mg/kg/天CNI-H 0294显著降低寄生虫血症> 90%。该化合物在小鼠中毒性低，腹腔注射LD 50为590 ± 66 mg/kg，血浆动力学快速。这些结果表明CNI-H 0294具有相当的抗疟活性，值得进一步研究。
Because of the spread of drug-resistantPlasmodiumspecies, there is an urgent need for novel effective antimalarial agents. A series of arylene bis(methylketone) compounds were screened in vitro against a number ofPlasmodium falciparumclones and in vivo againstPlasmodium berghei. 2-amino-4-(3,5-diacetylphenyl)amino-1,6-dimethylpyrimidinium chloride (Cytokine Network Inc. [CNI]-H0294) was the most effective of the compounds in vitro, with an IC50of 1.5–4.0 µ/Magainst parasite clones with a wide range of sensitivities to chloroquine and pyrimethamine. Other compounds in the series had in vitro IC50values of 20–25 µ/M. In a 4-day test for suppression ofP. bergheiparasitemia in vivo, 50 mg/kg/day CNI-H0294 significantly decreased parasitemia by >90%. The compound was found to have low toxicity in mice, with an LD50of 590 ± 66 mg/kg intraperitoneally, and rapid plasma kinetics. These results show that CNI-H0294 has considerable antimalarial activity and merits further study.