Institute of Pharmacy and Molecular Biotechnology, Ruprecht-Karls University Heidelberg, Im Neuenheimer Feld 364,69120 Heidelberg, Germany.
Curr Med Chem. 2010;17(15):1594-617. doi: 10.2174/092986710790979953.
Parasitic diseases such as Kala azar (visceral leishmaniasis), Chagas disease human (American trypanosomiasis) and African sleeping sickness (African trypanosomiasis) are affecting more than 27 million people worldwide. They are categorized amongst the most important neglected diseases causing approximately 150,000 deaths annually. As no vaccination is available, treatment is solely dependent on chemotherapeutic drugs. This review provides a comprehensive insight into the treatment of Kala azar, Chagas disease and African sleeping sickness. In addition to established drugs, novel small molecule- based therapeutic approaches are discussed. Drugs currently used for the treatment of Kala azar include pentavalent antimonials, Amphotericin B, Miltefosine, and Paromomycin. Liposomal formulations such as AmBisome provide promising alternatives. Furthermore, antiproliferative compounds might open new avenues in Kala azar treatment. Regarding Chagas disease, chemotherapy is based on two drugs, Nifurtimox and Benznidazole. However, sequencing of T. cruzi genome in the year 2005 raises a hope for new drug targets. Proteases, sterols and sialic acids are potential promising drug targets. Suramin, Pentamidine, Melarsporol and Eflornithine are well-established drugs to treat African sleeping sickness. New treatment options include combination therapy of Eflornithine and Nifurtimox, a Chagas disease therapeutic.. However, all approved chemotherapeutic compounds for trypanosomatid diseases suffer from high toxicity. Further, increasing resistance limits their efficacy and compliance.
寄生虫病，如黑热病（内脏利什曼病）、恰加斯病（美洲锥虫病）和非洲昏睡病（非洲锥虫病），正在影响全球超过 2700 万人。它们被归类为最重要的被忽视疾病之一，每年导致约 15 万人死亡。由于没有疫苗，治疗完全依赖于化学疗法药物。本综述全面介绍了黑热病、恰加斯病和非洲昏睡病的治疗方法。除了已有的药物外，还讨论了新型基于小分子的治疗方法。目前用于治疗黑热病的药物包括五价锑、两性霉素 B、米替福新和巴龙霉素。阿霉素等脂质体制剂提供了有前途的替代品。此外，抗增殖化合物可能为黑热病治疗开辟新途径。关于恰加斯病，化疗基于两种药物，硝呋莫司和苯硝唑。然而，2005 年对 T. cruzi 基因组的测序带来了新的药物靶点的希望。蛋白酶、甾醇和唾液酸是有前途的潜在药物靶点。苏拉明、喷他脒、美拉胂醇和依氟鸟氨酸是治疗非洲昏睡病的成熟药物。新的治疗选择包括依氟鸟氨酸和硝呋莫司联合治疗，一种恰加斯病治疗方法。然而，所有批准用于治疗利什曼原虫病的化学疗法药物都具有很高的毒性。此外，耐药性的增加限制了它们的疗效和顺应性。
