Evaluation of azasterols as anti-parasitics
Evaluation of azasterols as anti-parasitics
复制标题
DOI：
10.1021/jm060290f
复制
发表时间：
2006-10-05
影响因子：
7.3
通讯作者：
Gilbert, Ian H.
中科院分区：
文献类型：
--
作者：
Gros, Ludovic;Lorente, Silvia Orenes;Gilbert, Ian H.
本文介绍了几种新型氮杂甾类化合物的设计、合成及其对布氏锥虫、罗得西亚锥虫、黑锥虫和黑锥虫的毒力评价。克氏锥虫、杜氏利什曼原虫和恶性疟原虫，它们分别是人类非洲锥虫病、恰加斯病、利什曼病和疟疾的病原体。部分化合物具有抗寄生虫活性。特别是，许多化合物似乎非常有效地抑制了T型血细胞的生长。B. rhodesiense，其中一种化合物的IC 50值为12 nM。可以辨别出清晰的结构活性关系。这些化合物代表了进一步优化的重要线索。氮杂甾醇以前已被证明能抑制T. cruzi和L. donovani通过抑制酶甾醇24-甲基转移酶。然而，在这种情况下，没有一种化合物显示出对酶的抑制。因此，这些化合物具有未知的作用模式。
In this article, the design and synthesis of some novel azasterols is described, followed by their evaluation against Trypanosoma brucei rhodesiense, T. cruzi, Leishmania donovani, and Plasmodium falciparum, the causative agents of human African trypanosomiasis, Chagas disease, leishmaniasis, and malaria, respectively. Some of the compounds showed anti-parasitic activity. In particular, a number of compounds appeared to very potently inhibit the growth of the blood stream form T. b. rhodesiense, with one compound giving an IC50 value of 12 nM. Clear structure activity relationships could be discerned. These compounds represent important leads for further optimization. Azasterols have previously been shown to inhibit sterol biosynthesis in T. cruzi and L. donovani by the inhibition of the enzyme sterol 24-methyltransferase. However, in this case, none of the compounds showed inhibition of the enzyme. Therefore, these compounds have an unknown mode of action.