Studies on the mechanism of antimalarial action of a novel arylene bis(methylketone).
Studies on the mechanism of antimalarial action of a novel arylene bis(methylketone).
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新型亚芳基双甲基酮的抗疟作用机制研究。
DOI：
10.1016/s0006-2952(97)00255-4
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发表时间：
1997
影响因子：
5.8
通讯作者：
Ulrich,P
中科院分区：
文献类型：
--
作者：
Berger,BJ;Dai,WW;Cerami,A;Ulrich,P
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（CNI-H 0294）是一种新的亚芳基双（甲基酮）化合物，其对氯喹和乙胺嘧啶抗性恶性疟原虫克隆显示抗疟活性。发现该化合物浓缩到感染的红细胞中，当寄生虫在1.0 μM CNI-H 0294-未感染的红细胞存在下培养时，积累了80-179 μM，相比之下，在相同条件下仅积累了2.5-3.4 μM CNI-H 0294。使用许多寄生虫克隆的线粒体后上清液，发现该化合物可抑制二氢叶酸还原酶（EC 1.5.1.3）活性，IC 50为243-483 μM。因此，虽然CNI-H 0294不是疟原虫二氢叶酸还原酶的强效抑制剂，但当与体外抗寄生虫生长的外部ED 50浓度相关时，化合物在感染红细胞中的积累达到足以抑制疟疾酶的浓度。
2-Amino-4-(3,5-diacetylphenyl)amino-l,6-dimethylpyrimidinium chloride (CNI-H0294) is a novel arylene bis(methylketone) compound that displays antimalarial activity against chloroquine- and pyrimethamine-resistant Plasmodium falciparum clones. The compound has been found to be concentrated into infected erythrocytes, with 80–179 μM accumulated when parasites were cultured in the presence of 1.0 μM CNI-H0294-Uninfected erythrocytes, in contrast, only accumulated 2.5–3.4 μM CNI-H0294 under identical conditions. Using postmitochondrial supernatants from a number of parasite clones, the compound was found to inhibit dihydrofolate reductase (EC 1.5.1.3) activity with an IC50of 243–483 μM. Thus, while CNI-H0294 is not a powerful inhibitor of plasmodial dihydrofolate reductase, the accumulation of the compound into infected erythrocytes, when correlated to the external ED50concentration against parasite growth in vitro, reaches concentrations sufficient to inhibit the malarial enzyme.