Development of new therapeutic reagents for trypanosoma disease based on the irreversible enzyme inhibition mechanism

由原生动物克氏锥虫引起的心脏病，是查尔加斯病的病原体，是拉丁美洲流行地区的主要死亡原因。自从硝呋莫司和苯硝唑被批准作为治疗该疾病的试剂以来，其疗效有限，并有严重的副作用和毒性报道。我们与里约热内卢大学的一个团队合作研究发现，一些基于自杀底物的唾液酸酶衍生物成为治疗查尔加斯病相关传染病的药物的一类新的先导化合物。在本研究中，我们的目标是建立在纳米颗粒表面组装自杀底物基衍生物的通用方案，这些纳米颗粒可以转化为具有实际应用前景的候选治疗试剂，如“纳米药物”。

Cardiopathy caused by the protozoan Trypanosoma cruzi, the etiologic agent of Chargas' disease, is the main cause of death in endemic regions of Latin America. Since nifurtimox and benznidazole are approved as therapeutic reagents for this disease, the efficacy is limited and serious side effects and toxicity were reported. Therefore, advent of novel therapeutic reagents has been strongly required.We have discovered by collaborative research with a team at University of Rio de Janeiro that some suicide substrate-based derivatives of sialidases become a new class of leads toward drugs for the treatment of infectious diseases related to the Chargas' disease. In the present study, we aimed to establish for the general protocol for the assembling suicide substrate-based derivatives on the surface of nanoparticles that can convert into practically promising level of therapeutic reagents candidates as "nanomedicine".