Rodriques Coura José, de Castro Solange L
Departamento de Medicina Tropical, Instituto Oswaldo Cruz-Fiocruz, Av. Brasil 4365, 21045-900 Rio de Janeiro, RJ, Brasil.
Mem Inst Oswaldo Cruz. 2002 Jan;97(1):3-24. doi: 10.1590/s0074-02762002000100001.
In this "Critical Review" we made a historical introduction of drugs assayed against Chagas disease beginning in 1912 with the works of Mayer and Rocha Lima up to the experimental use of nitrofurazone. In the beginning of the 70s, nifurtimox and benznidazole were introduced for clinical treatment, but results showed a great variability and there is still a controversy about their use for chronic cases. After the introduction of these nitroheterocycles only a few compounds were assayed in chagasic patients. The great advances in vector control in the South Cone countries, and the demonstration of parasite in chronic patients indicated the urgency to discuss the etiologic treatment during this phase, reinforcing the need to find drugs with more efficacy and less toxicity. We also review potential targets in the parasite and present a survey about new classes of synthetic and natural compounds studied after 1992/1993, with which we intend to give to the reader a general view about experimental studies in the area of the chemotherapy of Chagas disease, complementing the previous papers of Brener (1979) and De Castro (1993).
在这篇“批判性综述”中,我们对用于治疗恰加斯病的药物进行了历史介绍,时间跨度从1912年迈尔和罗查·利马的研究开始,直至硝呋烯腙的实验性应用。20世纪70年代初,硝呋替莫和苯硝唑被引入临床治疗,但结果显示差异很大,关于它们在慢性病例中的应用仍存在争议。在引入这些硝基杂环化合物后,仅有少数化合物在恰加斯病患者中进行了试验。南锥体国家在病媒控制方面取得了巨大进展,并且在慢性患者体内发现了寄生虫,这表明在此阶段讨论病因治疗的紧迫性,进一步凸显了寻找疗效更高、毒性更低药物的必要性。我们还综述了寄生虫的潜在靶点,并介绍了1992/1993年之后研究的新型合成和天然化合物,旨在让读者对恰加斯病化疗领域的实验研究有一个总体了解,作为对布雷纳(1979年)和德卡斯特罗(1993年)之前论文的补充。