Abstract: Malaria is a major global health problem that causes significant mortality and morbidity annually. The therapeutic options are scarce and massively challenged by the emergence of resistant parasite strains, which causes a major obstacle to malaria control. To prevent a potential public health emergency, there is an urgent need for new antimalarial drugs, with single-dose cures, broad therapeutic potential, and novel mechanism of action. Antimalarial drug development can follow several approaches ranging from modifications of existing agents to the design of novel agents that act against novel targets. Modern advancement in the biology of the parasite and the availability of the different genomic techniques provide a wide range of novel targets in the development of new therapy. Several promising targets for drug intervention have been revealed in recent years. Therefore, this review focuses on the progress made on the latest scientific and technological advances in the discovery and development of novel antimalarial agents. Among the most interesting antimalarial target proteins currently studied are proteases, protein kinases, Plasmodium sugar transporter inhibitor, aquaporin-3 inhibitor, choline transport inhibitor, dihydroorotate dehydrogenase inhibitor, isoprenoid biosynthesis inhibitor, farnesyltransferase inhibitor and enzymes are involved in lipid metabolism and DNA replication. This review summarizes the novel molecular targets and their inhibitors for antimalarial drug development approaches.

Keywords: drug resistance, novel targets, antimalarial agents, mode of action, Plasmodium


中文翻译：

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新靶点抗疟新药研发最新进展


摘要：疟疾是全球主要的健康问题，每年造成大量的死亡率和发病率。治疗选择稀缺，并且由于耐药寄生虫菌株的出现而受到巨大挑战，这对疟疾控制造成了重大障碍。为了预防潜在的突发公共卫生事件，迫切需要具有单剂量治愈、广泛治疗潜力和新颖作用机制的新型抗疟药物。抗疟药物的开发可以遵循多种方法，从修改现有药物到设计针对新靶点的新药物。寄生虫生物学的现代进步和不同基因组技术的可用性为新疗法的开发提供了广泛的新靶标。近年来已经揭示了几个有希望的药物干预目标。因此，本文重点关注新型抗疟药物发现和开发方面的最新科学技术进展。目前研究的最有趣的抗疟靶蛋白包括蛋白酶、蛋白激酶、疟原虫糖转运蛋白抑制剂、水通道蛋白-3抑制剂、胆碱转运抑制剂、二氢乳清酸脱氢酶抑制剂、类异戊二烯生物合成抑制剂、法呢基转移酶抑制剂以及参与脂质代谢和DNA复制的酶。本综述总结了抗疟药物开发方法的新分子靶点及其抑制剂。


关键词：耐药性、新靶点、抗疟药物、作用方式、疟原虫