Development of Specific Inhibitors of Parasitic Enzymes

寄生虫病，如疟疾、血吸虫病、丝虫病、利什曼病和美洲锥虫病(Chaga？S病)是一个重大的公共卫生问题，特别是在世界的热带和亚热带地区。在儿童中，它们会导致死亡或生长受损，在成人中会导致使人衰弱的慢性疾病。在许多工业化国家，人们也日益认识到这些寄生虫感染是造成慢性疾病的原因。目前没有可用于治疗任何人类寄生虫感染的疫苗。此外，由于耐药菌株的传播，目前使用的药物正在变得不那么有效。血吸虫病是仅次于疟疾的第二大流行寄生虫病，是世界许多地区严重发病和死亡的主要原因。这种疾病是由扁虫或血吸虫引起的，它们的卵会间接损害感染者的肝脏和脾脏。这些寄生虫以人体红细胞为食，并以血红蛋白为主要食物来源。我们的合作小组（Brindley, Abbenante, Fairlie）已经确定了两种酶，这些扁形虫需要使用它们来吃掉红细胞。该项目旨在开发能够阻止这些酶发挥作用的化合物。将对这些化合物进行测试，看它们是否能导致寄生虫饿死。如果成功的话，这些新化合物可以用作治疗这种疾病的药物，并且这种总体策略可以应用于其他吸血寄生虫。

Parasitic diseases such as malaria, schistosomiasis, filariasis, leishmaniasis, and american trypanosomiasis (Chaga?s disease) are a significant public health issue, especially in tropical and subtropical regions of the world. In children, they cause death or impaired growth and in adults debilitating chronic illness. These parasitic infections are increasingly being recognized as responsible for chronic illness in many industrialized countries as well. There are no vaccines currently available for the treatment of any of the human parasitic infections. In addition, the drugs that are currently used are becoming less effective because of the spread of drug resistant strains. Schistosomiasis, is the second most prevalent parasitic disease, after malaria, and is a leading cause of severe morbidity and death in many parts of the world. The disease is caused by flatworms or blood flukes, the eggs of which indirectly cause damage to the liver and spleen of infected individuals. These parasites feed on human red blood cells and use hemoglobin as their major food source. Our collaborative team (Brindley, Abbenante, Fairlie) has identified two enzymes that these flatworms need to use to eat red blood cells. This project aims to develop compounds that will stop these enzymes from functioning. These compounds will be tested to see whether they can cause the parasites to die of starvation. If successful these new compounds can be used as drugs to treat the disease and the general strategy can be applied to other blood-feeding parasites.