Cerecetto Hugo, González Mercedes
Departamento de Química Orgánica, Facultad de Química y Facultad de Ciencias, Universidad de la República, Iguá 4225, 11400 Montevideo, Uruguay.
Mini Rev Med Chem. 2008 Nov;8(13):1355-83. doi: 10.2174/138955708786369528.
Chagas' disease is the major endemic disease in South and Central America caused by a trypanosomatid parasite (Trypanosoma cruzi). The current treatment relies on two old and non-specific chemotherapeutic agents, Nifurtimox and Benznidazole. Despite the major advances that have been made in the identification of specific targets that afford selectivity, the drugs used today have serious side effects. Furthermore, differences in drug susceptibility among different T. cruzi isolates have led to varied parasitological cure rates depending on the geographical region. There is, therefore, an urgent need for the development of new antichagasic drugs. In this regard we have spent more than a decade in the search for more effective agents able to compromise the proliferation of T. cruzi. We began our research with our own compounds and then continued with compounds from other researcher groups. We systematically characterized representatives of a wide range of different chemical families. In this review we summarize our ongoing efforts to identify potential anti-T. cruzi agents using our compound-library. It is discussed and presented the structure-activity relationship observed among the different groups of chemical families.
恰加斯病是南美洲和中美洲由锥虫寄生虫(克氏锥虫)引起的主要地方病。目前的治疗依赖于两种古老且无特异性的化疗药物,硝呋莫司和苯硝唑。尽管在确定具有选择性的特定靶点方面取得了重大进展,但如今使用的药物有严重的副作用。此外,不同克氏锥虫分离株之间的药物敏感性差异导致根据地理区域不同,寄生虫学治愈率也有所不同。因此,迫切需要开发新的抗恰加斯病药物。在这方面,我们花了十多年时间寻找能够抑制克氏锥虫增殖的更有效药物。我们从自己的化合物开始研究,然后继续研究其他研究团队的化合物。我们系统地表征了广泛不同化学家族的代表。在这篇综述中,我们总结了我们目前使用化合物库鉴定潜在抗克氏锥虫药物的工作。讨论并展示了在不同化学家族组中观察到的构效关系。