恰加斯病是由原生动物寄生虫克氏锥虫引起的一种被忽视的热带病,危及全世界近7000万人。目前唯一被批准用于其治疗的两种药物,苯并咪唑和硝呋替莫,在成人中有争议的疗效和限制安全问题,让成千上万的病人得不到合适的治疗.对恰加斯病的忽视进一步说明了缺乏新化学实体的强大而多样的药物发现和开发组合。建立强大的抗chagasic药物研发网络至关重要。专注于由拉丁美洲科学家领导的药物发现计划,这种疾病的主要流行地区,我们在这里讨论了在过去十年中发表的关于鉴定新的抗寄生虫药物来治疗查加斯病的内容,聚光灯照耀着原点,化学多样性,命中的表征水平,以及用于优化铅化合物的策略。最后,我们确定了这些药物发现活动的优势和劣势,并强调了多学科合作和知识共享的重要性。
Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi that endangers almost 70 million people worldwide. The only two drugs that are currently approved for its treatment, benznidazole and nifurtimox, have controversial efficacy in adults and restricting safety issues, leaving thousands of patients without a suitable treatment. The neglect of Chagas disease is further illustrated by the lack of a robust and diverse drug discovery and development portfolio of new chemical entities, and it is of paramount importance to build a strong research and development network for antichagasic drugs. Focusing on drug discovery programs led by scientists based in Latin America, the main endemic region for this disease, we discuss herein what has been published in the last decade in terms of identification of new antiparasitic drugs to treat Chagas disease, shining a spotlight on the origin, chemical diversity, level of characterization of hits, and strategies used for optimization of lead compounds. Finally, we identify strengths and weaknesses in these drug discovery campaigns and highlight the importance of multidisciplinary collaboration and knowledge sharing.