Research Unit for Tropical Diseases, de Duve Institute and Laboratory of Biochemistry, Université catholique de Louvain, Brussels, Belgium.
Planta Med. 2011 Apr;77(6):586-97. doi: 10.1055/s-0030-1250411. Epub 2010 Oct 13.
Trypanosoma brucei is the causative agent of human African trypanosomiasis (sleeping sickness) which is fatal if left untreated. This disease occurs in 36 African countries, south of the Sahara, where 60 million people are at risk of acquiring infection. The current chemotherapy relies on only four drugs, three of which were developed more than 60 years ago. These drugs have many limitations, ranging from oral inabsorption, acute toxicities, short duration of action and the emergence of trypanosomal resistance. Despite decades of use of most of the current trypanocides, little is known about their mode of action. That being said, African trypanosomes continue to be among the most extensively studied parasitic protists to date. Many of their intriguing biological features have been well documented and can be viewed as attractive targets for antitrypanosomal chemotherapy. A considerable number of natural products with diverse molecular structures have revealed antiparasitic potency in the laboratory and represent interesting lead compounds for the development of new and urgently needed antiparasitics. The major validated drug targets in T. brucei are discussed with particular emphasis on those known to be attacked by natural compounds.
布氏锥虫是引起人类非洲锥虫病（昏睡病）的病原体，如果不治疗则是致命的。该病发生在撒哈拉以南的 36 个非洲国家，有 6000 万人面临感染风险。目前的化疗仅依赖于四种药物，其中三种是 60 多年前开发的。这些药物有许多局限性，包括口服吸收不良、急性毒性、作用时间短以及寄生虫耐药性的出现。尽管目前大多数的抗锥虫药物已经使用了几十年，但人们对它们的作用机制知之甚少。也就是说，非洲锥虫仍然是迄今为止研究最多的寄生原生动物之一。它们许多有趣的生物学特征已经得到了很好的记录，并且可以被视为抗锥虫化疗的有吸引力的靶点。大量具有不同分子结构的天然产物在实验室中显示出抗寄生虫活性，它们是开发新的、急需的抗寄生虫药物的有趣先导化合物。本文特别强调了那些已知被天然化合物攻击的靶标，讨论了在布氏锥虫中得到验证的主要药物靶标。
