Soeiro Maria de Nazaré C, de Castro Solange Lisboa
Laboratório de Biologia Celular, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, 21040-900, Brazil.
Open Med Chem J. 2011;5:21-30. doi: 10.2174/1874104501105010021. Epub 2011 Mar 9.
Chagas disease (CD), caused by the intracellular protozoan Trypanosoma cruzi, is a parasitic illness endemic in Latin America. In the centennial after CD discovery by Carlos Chagas (1909), although it still represents an important public health problem in these affected areas, the existing chemotherapy, based on benznidazole and nifurtimox (both introduced more than four decades ago), is far from being considered ideal due to substantial toxicity, variable effect on different parasite stocks and well-known poor activity on the chronic phase. CD is considered one of the major "neglected" diseases of the world, as commercial incentives are very limited to guarantee investments for developing and discovering novel drugs. In this context, our group has been pursuing, over the last years, the efficacy, selectivity, toxicity, cellular targets and mechanisms of action of new potential anti-T. cruzi candidates screened from an in-house compound library of different research groups in the area of medicinal chemistry. A brief review regarding these studies will be discussed, mainly related to the effect on T. cruzi of (i) diamidines and related compounds, (ii) natural naphthoquinone derivatives, and (iii) megazol derivatives.
恰加斯病（CD）由细胞内原生动物克氏锥虫引起，是拉丁美洲特有的一种寄生虫病。在卡洛斯·恰加斯于1909年发现恰加斯病后的百年间，尽管在这些受影响地区它仍是一个重要的公共卫生问题，但现有的基于苯并硝唑和硝呋莫司（两者均于四十多年前推出）的化疗方法，由于毒性大、对不同寄生虫株的效果各异以及在慢性期众所周知的疗效不佳，远非理想的治疗方法。恰加斯病被认为是世界上主要的“被忽视”疾病之一，因为商业激励措施非常有限，无法保证对开发和发现新型药物的投资。在此背景下，我们团队在过去几年中一直在研究从药物化学领域不同研究小组的内部化合物库中筛选出的新型潜在抗克氏锥虫候选药物的疗效、选择性、毒性、细胞靶点和作用机制。将对这些研究的简要综述将展开讨论，主要涉及（i）双脒及相关化合物、（ii）天然萘醌衍生物和（iii）美拉唑衍生物对克氏锥虫的影响。
