Trypanocidal drugs targeting PFK and PYK

原生动物寄生虫是发展中国家严重疾病的原因，每年有数百万人处于危险之中，数万人死亡。目前的治疗方法很差，使用毒性很大的药物。寄生虫有一个相当独特的代谢糖的生化途径。我们已经鉴定了参与该途径的两种蛋白质，并利用这些信息设计和合成了阻断该途径的药物样分子库。我们的初步试验还表明，这些化合物中的一些可以杀死寄生虫，并且与哺乳动物细胞相比，对寄生虫具有特异性。这些结果为开发可作为潜在药物进行测试的更有效和特异性的分子家族提供了一个很好的起点。我们的方法将导致两个互补的药物家族，这可能为联合治疗提供基础，不仅更有效，而且还将寄生虫群体中产生耐药性的风险降至最低。

Protozoan parasites are the cause of serious diseases of the developing world where literally millions of people are at risk and tens of thousands die annually. Current treatments are poor and use very toxic drugs. The parasites have a rather unique biochemical pathway for metabolising sugar. We have characterised two proteins involved in this pathway and have used this information to design and synthesise libraries of drug-like molecules that block the pathway. Our initial trials also show that some of these compounds kill the parasite and show specificity against the parasite compared to mammalian cells. These results provide an excellent starting point for developing more potent and specific molecular families that can be tested as potential drugs. Our approach will lead to two complementary drug families that may provide the basis of a combination therapy that would not only be more potent, but also minimise the risk of the development of resistance in the parasite population.