Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum:: A potential route to chemotherapy
Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum:: A potential route to chemotherapy
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DOI：
10.1021/jm0002578
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发表时间：
2001-03-15
影响因子：
7.3
通讯作者：
Oldfield, E
中科院分区：
文献类型：
--
作者：
Martin, MB;Grimley, JS;Oldfield, E
我们在体外研究了一系列双膦酸盐对克氏锥虫、罗得西亚布氏锥虫、杜氏利什曼原虫、弓形虫和恶性疟原虫增殖的影响。结果表明，骨吸收治疗中使用的含氮双膦酸盐对寄生虫具有显着的活性，在某些情况下，芳香族物质对寄生虫复制具有纳摩尔或低微摩尔的 IC50 活性值（例如邻利塞膦酸盐，对于罗得西亚布氏弓形虫，IC50 = 220 nM；利塞膦酸盐，对于弓形虫，IC50 = 490 nM）。在克氏锥虫中，含氮二膦酸盐利塞膦酸盐可在前角鲨烯水平上抑制甾醇生物合成，很可能是通过抑制法尼基焦磷酸合酶来实现的。因此，双膦酸盐似乎具有治疗寄生性原生动物疾病的潜力。
We have investigated the effects in vitro of a series of bisphosphonates on the proliferation of Trypanosoma cruzi, Trypanosoma brucei rhodesiense, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum. The results show that nitrogen-containing bisphosphonates of the type used in bone resorption therapy have significant activity against parasites, with the aromatic species having in some cases nanomolar or low-micromolar IC50 activity values against parasite replication (e.g. o-risedronate, IC50 = 220 nM for T. brucei rhodesiense; risedronate, IC50 = 490 nM for T. gondii). In T. cruzi, the nitrogen-containing bisphosphonate risedronate is shown to inhibit sterol biosynthesis at a pre-squalene level, most likely by inhibiting farnesylpyrophosphate synthase. Bisphosphonates therefore appear to have potential in treating parasitic protozoan diseases.