人类非洲锥虫病的治疗研究进展

Progress in the Treatment of Human African Trypanosomiasis

人类非洲锥虫病是一种被忽视的热带寄生虫病,威胁着撒哈拉以南非洲人民的生命健康。目前临床使用的治疗药物有四种,这些药物副作用多,用药困难并产生了一定的耐药性,因此有必要开发安全有效且利于服用的药物。目前有三类候选药物相继进入临床实验阶段,在不久的将来可能会进入临床应用。另外,还有许多正在研究的治疗药物,包括天然产物、磷酸二酯酶抑制剂、蛋白酶抑制剂、拓扑异构酶抑制剂、亮氨酰t RNA合成酶抑制剂、微管蛋白抑制剂以及一些靶点尚不明确却有很好的锥虫抑制活性的化合物。其中,壳二孢呋喃酮选择性较好,喹啉-3-羧酸类衍生物毒性低,5-硝基-2-呋喃酰胺类化合物对硝呋莫司耐受的锥虫仍有活性。这些研究无疑都为新型抗锥虫药物的出现提供了可能,相信在不久的将来越来越多的药物会在临床使用。

Human African Trypanosomiasis is one of the neglected diseases in tropics and threatens millions of people of sub-Sahara Africa. Currently, there are four drugs approved for the treatment of HAT, these drugs are limited for unacceptable toxicities,difficult in administers and increasing tolerances. Therefore, highly effective and safe agents for the treatment of HAT are urgently needed. There are three types of new drug candidates have entered clinical trials. In addition, there are a lot of new medications in study,including natural products, phosphodiesterase inhibitors, protease inhibitors, topoisomerase inhibitors, leucyl-t RNA synthetase inhibitors,microtubule protein inhibitor as well as some compounds with good Trypanosoma inhibitory activity but without clear targets.Ascofuranone had a good selectivity, quinoline-3-carboxylic acid derivatives were low toxicity, 5-nitro-2-furancarboxylamides were still active to nifurtimox-resistant cells. These studies make the emergence of new antitrypanosomal agents possible, we believe that more and more drugs will be used in clinical in the near future.