College of Pharmacy, Gachon University of Medicine and Science, Hambakmoeiro, 191, Yeonsu-gu, Incheon 406-799, South Korea.
Laboratory of Organic and Medicinal Chemistry, Department of Chemistry, Malaviya National Institute of Technology, Jawaharlal Nehru Marg, Jaipur-302017, India.
Curr Top Med Chem. 2019;19(10):861-873. doi: 10.2174/1568026619666190603080000.
The malaria parasite resistance to the existing drugs is a serious problem to the currently used antimalarials and, thus, highlights the urgent need to develop new and effective anti-malarial molecules. This could be achieved either by the identification of the new drugs for the validated targets or by further refining/improving the existing antimalarials; or by combining previously effective agents with new/existing drugs to have a synergistic effect that counters parasite resistance; or by identifying novel targets for the malarial chemotherapy. In this review article, a comprehensive collection of some of the novel molecular targets has been enlisted for the antimalarial drugs. The targets which could be deliberated for developing new anti-malarial drugs could be: membrane biosynthesis, mitochondrial system, apicoplasts, parasite transporters, shikimate pathway, hematin crystals, parasite proteases, glycolysis, isoprenoid synthesis, cell cycle control/cycline dependent kinase, redox system, nucleic acid metabolism, methionine cycle and the polyamines, folate metabolism, the helicases, erythrocyte G-protein, and farnesyl transferases. Modern genomic tools approaches such as structural biology and combinatorial chemistry, novel targets could be identified followed by drug development for drug resistant strains providing wide ranges of novel targets in the development of new therapy. The new approaches and targets mentioned in the manuscript provide a basis for the development of new unique strategies for antimalarial therapy with limited off-target effects in the near future.
疟原虫对现有药物的抗药性是目前使用的抗疟药物的一个严重问题，因此，迫切需要开发新的有效抗疟药物。这可以通过鉴定新的药物来实现针对已验证的靶点，或者通过进一步改进/优化现有的抗疟药物；或者通过将以前有效的药物与新的/现有的药物联合使用，产生协同作用，以对抗寄生虫的耐药性；或者通过确定新的抗疟化疗靶点。在这篇综述文章中，我们列出了一些针对抗疟药物的新的分子靶点。可以考虑用于开发新的抗疟药物的靶点有：膜生物合成、线粒体系统、类质体、寄生虫转运蛋白、莽草酸途径、血红素晶体、寄生虫蛋白酶、糖酵解、异戊烯合成、细胞周期控制/细胞周期依赖性激酶、氧化还原系统、核酸代谢、蛋氨酸循环和多胺、叶酸代谢、解旋酶、红细胞 G 蛋白和法呢基转移酶。现代基因组工具方法，如结构生物学和组合化学，可以识别新的靶点，然后针对耐药菌株进行药物开发，为新疗法的发展提供广泛的新靶点。本文提到的新方法和靶点为未来不久开发新的抗疟治疗方法提供了新的独特策略的基础，这些方法和靶点的副作用较小。
