Moraes Carolina B, Franco Caio H
a Laboratório Nacional de Biociências (LNBio) , Centro Nacional de Pesquisa em Energia e Materiais (CNPEM) , Campinas , Brazil.
b Graduate Program in Microbiology and Immunology , Universidade Federal de Sao Paulo , Sao Paulo , Brazil.
Expert Opin Drug Discov. 2016;11(5):447-55. doi: 10.1517/17460441.2016.1160883. Epub 2016 Apr 1.
Chagas disease is a chronic infection associated with long-term morbidity. Increased funding and advocacy for drug discovery for neglected diseases have prompted the introduction of several important technological advances, and Chagas disease is among the neglected conditions that has mostly benefited from technological developments. A number of screening campaigns, and the development of new and improved in vitro and in vivo assays, has led to advances in the field of drug discovery.
This review highlights the major advances in Chagas disease drug screening, and how these are being used not only to discover novel chemical entities and drug candidates, but also increase our knowledge about the disease and the parasite. Different methodologies used for compound screening and prioritization are discussed, as well as novel techniques for the investigation of these targets. The molecular mechanism of action is also discussed.
Technological advances have been executed with scientific rigour for the development of new in vitro cell-based assays and in vivo animal models, to bring about novel and better drugs for Chagas disease, as well as to increase our understanding of what are the necessary properties for a compound to be successful in the clinic. The gained knowledge, combined with new exciting approaches toward target deconvolution, will help identifying new targets for Chagas disease chemotherapy in the future.
恰加斯病是一种与长期发病相关的慢性感染。对被忽视疾病药物研发的资金投入增加和宣传力度加大,促使了多项重要技术进步的引入,恰加斯病是从技术发展中受益最多的被忽视疾病之一。一系列筛选活动以及新型和改进的体外及体内检测方法的开发,推动了药物研发领域的进展。
本综述重点介绍了恰加斯病药物筛选的主要进展,以及这些进展如何不仅用于发现新型化学实体和候选药物,还能增加我们对该疾病和寄生虫的了解。讨论了用于化合物筛选和优先级排序的不同方法,以及研究这些靶点的新技术。还讨论了作用的分子机制。
为开发新的基于细胞的体外检测方法和体内动物模型,已严谨地执行技术进步,以研发出针对恰加斯病的新型且更好的药物,并增进我们对化合物在临床上取得成功所需特性的理解。所获得的知识,结合针对靶点反卷积的新的令人兴奋的方法,将有助于未来确定恰加斯病化疗的新靶点。