Parasite mitochondria as a target of chemotherapy -: Inhibitory effect of licochalcone A on the Plasmodium falciparum respiratory chain
Parasite mitochondria as a target of chemotherapy -: Inhibitory effect of licochalcone A on the Plasmodium falciparum respiratory chain
复制标题
DOI：
10.1196/annals.1352.037
复制
发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Kita, K
中科院分区：
文献类型：
--
作者：
Mi-Ichi, F;Miyadera, H;Kita, K
寄生虫利用独特的能量代谢途径来适应自然宿主的栖息地。事实上，寄生虫的呼吸系统在电子传递途径上通常比宿主动物表现出更大的多样性。寄生虫线粒体和相关酶的这些独特方面可能代表有希望的化疗靶点。天然产物已被认为是这种寄生虫呼吸链的特异性抑制剂的候选者的来源。查耳酮最近在体外和体内评价其抗疟活性。然而，其在疟疾寄生虫中的靶点仍不清楚。在这项研究中，我们研究了甘草查尔酮A抑制BC，复合物（泛喹啉-细胞色素c还原酶）以及复合物II（琥珀酸泛醌还原酶，SQR）的恶性疟原虫线粒体。特别地，甘草查尔酮A在非常低的浓度下抑制bc复合物活性。由于恶性疟原虫bc（1）复合物的性质与哺乳动物宿主不同，查尔酮有望成为一种新的抗疟药物。
Parasites have exploited unique energy metabolic pathways as adaptations to the natural host habitat. In fact, the respiratory systems of parasites typically show greater diversity in electron transfer pathways than do those of host animals. These unique aspects of parasite mitochondria and related enzymes may represent promising targets for chemotherapy. Natural products have been recognized as a source of the candidates of the specific inhibitors for such parasite respiratory chains. Chalcones was recently evaluated for its antimalarial activity in vitro and in vivo. However, its target is still unclear in malaria parasites. In this study, we investigated that licochalcone A inhibited the bc, complex (ubiquinol-cytochrome c reductase) as well as complex II (succinate ubiquinone reductase, SQR) of Plasmodium falciparum mitochondria. In particular, licochalcone A inhibits bc, complex activity at very low concentrations. Because the property of the P. falciparum bc(1) complex is different from that of the mammalian host, chalcones would be a promising candidate for a new antimalarial drug.