Meier Anna, Erler Holger, Beitz Eric
Department of Pharmaceutical and Medicinal Chemistry, Christian-Albrechts-University of Kiel, Kiel, Germany.
Front Chem. 2018 Mar 27;6:88. doi: 10.3389/fchem.2018.00088. eCollection 2018.
Infectious diseases caused by pathogenic protozoa are among the most significant causes of death in humans. Therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains. Many of the current anti-parasite drugs target soluble enzymes, generate unspecific oxidative stress, or act by an unresolved mechanism within the parasite. In recent years, collections of drug-like compounds derived from large-scale phenotypic screenings, such as the or , have been made available to researchers free of charge boosting the identification of novel promising targets. Remarkably, several of the compound hits have been found to inhibit membrane proteins at the periphery of the parasites, i.e., channels and transporters for ions and metabolites. In this review, we will focus on the progress made on targeting channels and transporters at different levels and the potential for use against infections with apicomplexan parasites mainly spp. (malaria) and (toxoplasmosis), with kinetoplastids (sleeping sickness), (Chagas disease), and ssp. (leishmaniasis), and the amoeba (amoebiasis).
由致病性原生动物引起的传染病是人类死亡的最重要原因之一。治疗选择稀缺，且耐药寄生虫菌株的出现对其构成了巨大挑战。目前许多抗寄生虫药物靶向可溶性酶，产生非特异性氧化应激，或通过寄生虫体内未明确的机制起作用。近年来，通过大规模表型筛选获得的类药物化合物库，如[具体库名1]或[具体库名2]，已免费提供给研究人员，促进了新的有前景靶点的鉴定。值得注意的是，已发现一些命中化合物可抑制寄生虫外周的膜蛋白，即离子和代谢物的通道和转运体。在本综述中，我们将重点关注在不同水平上针对通道和转运体所取得的进展，以及针对主要由顶复门寄生虫[疟原虫属物种（疟疾）]和[弓形虫属（弓形虫病）]、动基体目寄生虫[布氏锥虫（昏睡病）]、[克氏锥虫（恰加斯病）]和[利什曼原虫属物种（利什曼病）]以及变形虫[溶组织内阿米巴（阿米巴病）]引起的感染的应用潜力。
