Berninger Michael, Schmidt Ines, Ponte-Sucre Alicia, Holzgrabe Ulrike
Institute of Pharmacy and Food Chemistry , University of Würzburg , Am Hubland , 97074 Würzburg , Germany . Email:
Laboratory of Molecular Physiology , Institute of Experimental Medicine , Luis Razetti School of Medicine , Faculty of Medicine , Universidad Central de Venezuela Caracas , Venezuela . Tel: +0931 31 85461.
Medchemcomm. 2017 Jul 31;8(10):1872-1890. doi: 10.1039/c7md00280g. eCollection 2017 Oct 1.
Human African trypanosomiasis (HAT), also known as African sleeping sickness, is caused by parasitic protozoa of the genus . As the disease progresses, the parasites cross the blood brain barrier and are lethal for the patients if the disease is left untreated. Current therapies suffer from several drawbacks due to toxicity of the respective compounds or resistance to approved antitrypanosomal drugs. In this review, the different strategies of drug development against HAT are considered, namely the target-based approach, the phenotypic high throughput screening and the drug repurposing strategy. The most promising compounds emerging from these approaches entering an evaluation are mentioned herein. Of note, it may turn out to be difficult to confirm activity in an animal model of infection; however, possible reasons for the missing efficacy in unsuccessful studies are discussed.
人类非洲锥虫病（HAT），也被称为非洲昏睡病，是由 属的寄生原生动物引起的。随着疾病的进展，寄生虫会穿过血脑屏障，如果不进行治疗，对患者来说是致命的。由于各自化合物的毒性或对已批准的抗锥虫药物的耐药性，目前的治疗方法存在几个缺点。在这篇综述中，考虑了针对HAT的不同药物开发策略，即基于靶点的方法、表型高通量筛选和药物再利用策略。本文提到了从这些进入 评估的方法中出现的最有前景的化合物。值得注意的是，可能很难在感染动物模型中确认 活性；然而，讨论了在不成功的 研究中疗效缺失的可能原因。
