Division of Infectious Diseases and Immunology, Indian Institute of Chemical Biology, 4, Raja S.C. Mullick Road, Jadavpur, Kolkata-700032, West Bengal, India.
Expert Rev Clin Pharmacol. 2009 Sep;2(5):469-89. doi: 10.1586/ecp.09.28.
Malaria is a major global threat, that results in more than 2 million deaths each year. The treatment of malaria is becoming extremely difficult due to the emergence of drug-resistant parasites, the absence of an effective vaccine, and the spread of insecticide-resistant vectors. Thus, malarial therapy needs new chemotherapeutic approaches leading to the search for new drug targets. Here, we discuss different approaches to identifying novel antimalarial drug targets. We have also given due attention to the existing validated targets with a view to develop novel, rationally designed lead molecules. Some of the important parasite proteins are claimed to be the targets; however, further in vitro or in vivo structure-function studies of such proteins are crucial to validate these proteins as suitable targets. The interactome analysis among apicoplast, mitochondrion and genomic DNA will also be useful in identifying vital pathways or proteins regulating critical pathways for parasite growth and survival, and could be attractive targets. Molecules responsible for parasite invasion to host erythrocytes and ion channels of infected erythrocytes, essential for intra-erythrocyte survival and stage progression of parasites are also becoming attractive targets. This review will discuss and highlight the current understanding regarding the potential antimalarial drug targets, which could be utilized to develop novel antimalarials.
疟疾是一个主要的全球性威胁,每年导致超过 200 万人死亡。由于抗药性寄生虫的出现、缺乏有效的疫苗以及抗杀虫剂媒介的传播,疟疾的治疗变得极其困难。因此,疟疾治疗需要新的化疗方法,从而寻找新的药物靶点。在这里,我们讨论了识别新的抗疟药物靶点的不同方法。我们也对现有的经过验证的靶点给予了应有的关注,以期开发新的、经过合理设计的先导分子。一些重要的寄生虫蛋白被认为是靶点;然而,这些蛋白作为合适靶点的进一步体外或体内结构功能研究至关重要。质体、线粒体和基因组 DNA 之间的互作组分析也将有助于识别调控寄生虫生长和存活的关键途径或蛋白质的重要途径,这些途径或蛋白质可能是有吸引力的靶点。负责寄生虫入侵宿主红细胞和感染红细胞离子通道的分子,对于红细胞内生存和寄生虫阶段进展至关重要,也成为有吸引力的靶点。这篇综述将讨论和强调目前对抗疟药物靶点的潜在理解,这些靶点可以用来开发新的抗疟药物。