Goodman Christopher D, Pasaje Charisse Flerida A, Kennedy Kit, McFadden Geoffrey I, Ralph Stuart A
School of Biosciences, The University of Melbourne, Melbourne, Victoria 3010, Australia.
Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Victoria 3010, Australia.
Trends Parasitol. 2016 Dec;32(12):953-965. doi: 10.1016/j.pt.2016.09.011. Epub 2016 Oct 25.
Antibiotics inhibiting protein translation have long been used to treat and prevent infections by apicomplexan parasites. These compounds kill parasites by inhibiting organellar translation, and most act specifically against the apicoplast, a relict plastid in apicomplexans. Drug resistance in Plasmodium and other apicomplexans dictates a need for development of novel targets. Some apicoplast inhibitors have a delayed onset of action, so they cannot replace fast-acting drugs, although they still fulfil important roles in treating and preventing infections. The plethora of bacterial-like actors in the translation machinery of parasite mitochondria and plastids presents validated targets with strong potential for selectivity. Here we discuss existing drugs that inhibit organellar translation, and explore targets that may be further exploited in antiparasitic drug design.
长期以来,抑制蛋白质翻译的抗生素一直被用于治疗和预防顶复门寄生虫感染。这些化合物通过抑制细胞器翻译来杀死寄生虫,并且大多数特异性作用于顶质体,即顶复门生物中的一种残留质体。疟原虫和其他顶复门生物中的耐药性表明需要开发新的靶点。一些顶质体抑制剂起效延迟,因此尽管它们在治疗和预防感染中仍发挥重要作用,但无法替代速效药物。寄生虫线粒体和质体翻译机制中大量类似细菌的成分提供了经过验证且具有很强选择性潜力的靶点。在此,我们讨论现有的抑制细胞器翻译的药物,并探索在抗寄生虫药物设计中可能进一步开发利用的靶点。