Trypanocidal drugs targeting PFK and PYK

针对 PFK 和 PYK 的杀锥虫药物

• 批准号: G0600014/1
• 负责人: Malcolm Walkinshaw
• 金额: $ 40.37万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2007
• 资助国家: 英国
• 起止时间: 2007 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=G0600014%2F1
• 关键词: Trypanocidal; drugs; targeting; PFK; PYK

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.

原生动物寄生虫是导致发展中国家严重疾病的原因，那里每年有数以百万计的人处于危险之中，数万人死亡。目前的治疗方法很差，而且使用的药物毒性很大。这种寄生虫有一种相当独特的生化途径来代谢糖。我们已经描述了参与这一途径的两种蛋白质，并利用这些信息设计和合成了阻断这一途径的类药物分子文库。我们的初步试验还表明，与哺乳动物细胞相比，这些化合物中的一些可以杀死寄生虫，并表现出对寄生虫的特异性。这些结果为开发更有效和特异的分子家族提供了一个很好的起点，这些分子家族可以作为潜在的药物进行测试。我们的方法将导致两个互补的药物家族，它们可能为联合治疗提供基础，这种联合治疗不仅更有效，而且还将寄生虫种群中产生耐药性的风险降至最低。