Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Sir James Black Centre, Dundee, DD1 5EH, UK.
Bioorg Med Chem. 2010 Oct 15;18(20):7291-301. doi: 10.1016/j.bmc.2010.08.007. Epub 2010 Aug 9.
We have previously shown that azasterols have activity against Trypanosoma brucei, Trypanosoma cruzi and Leishmania species, which are the causative agents of various neglected tropical diseases. In this paper, we discuss the replacement of the sterol core of the azasterols with sterol mimics. Various mimics were designed, and the structures were minimised to see if they could adopt a similar conformation to that of the azasterols. From this, two series of mimics were synthesised and then evaluated against the parasites. Compounds showed moderate activity.
我们之前已经证明,氮杂甾醇类化合物对引起各种热带病的病原体,包括布氏锥虫、克氏锥虫和利什曼原虫,具有活性。在本文中,我们讨论了用甾醇类似物替代氮杂甾醇类化合物的甾醇核心。设计了各种类似物,并对其结构进行了最小化处理,以观察它们是否可以采用类似于氮杂甾醇类化合物的构象。由此,合成了两个系列的类似物,并对其进行了抗寄生虫活性评价。结果表明,部分化合物具有中等活性。