Choi Seoung-Ryoung, Mukherjee Prasenjit, Avery Mitchell A
Department of Medicinal Chemistry, University of Mississippi, University, MS 38677, USA.
Curr Med Chem. 2008;15(2):161-71. doi: 10.2174/092986708783330575.
Malaria, one of the major reemerging parasitic diseases, is caused by protozoal parasites belonging to the genus plasmodia. Antimalarial drugs have played a mainstream role in controlling the spread of malaria through the treatment of patients infected with the plasmodial parasites and controlling its transmissibility. The current line of therapy against malaria is faced with the hurdles of a low or total lack of efficacy due to the evolution of drug-resistant strains of the malarial parasites. Preventive vaccination against malaria is an ideal solution to this problem but is not expected to arrive for at least a decade. Development of antimalarial drugs involving novel mechanisms of action is therefore of imminent importance. Several novel drug candidates of synthetic and natural products origin as well as their combination therapies are currently being evaluated for their efficacy against the drug-resistant strains of the parasites. Various plasmodial targets/pathways, such as the Purine salvage pathway, Pyrimidine biosynthesis pathway as well as the processes in the apicoplast, have been identified and are being utilized for the discovery and development of novel antimalarial therapies. This review provides an overview of the latest developments in terms of drugs, combination therapies and novel plasmodial targets being carried out to counter the menace of drug-resistant malaria.
疟疾是主要的重新出现的寄生虫病之一，由疟原虫属的原生动物寄生虫引起。抗疟药物通过治疗感染疟原虫的患者并控制其传播性，在控制疟疾传播方面发挥了主流作用。由于疟原虫耐药菌株的进化，目前的疟疾治疗方法面临疗效低下或完全无效的障碍。疟疾预防性疫苗接种是解决这一问题的理想方法，但预计至少十年内无法实现。因此，开发具有新作用机制的抗疟药物迫在眉睫。目前正在评估几种合成和天然产物来源的新型候选药物及其联合疗法对寄生虫耐药菌株的疗效。已经确定了各种疟原虫靶点/途径，如嘌呤补救途径、嘧啶生物合成途径以及顶质体中的过程，并正在将其用于发现和开发新型抗疟疗法。本综述概述了为应对耐药疟疾的威胁而在药物、联合疗法和新型疟原虫靶点方面的最新进展。
