Ionophores as Potent Anti-malarials: A Miracle in the Making

Plasmodium has a complex life cycle that spans between mosquito and human. For survival and pathogenesis it banks upon dynamic alterations in ionic transport across organelle and plasma membrane. Being a fundamental contributor of crucial biological processes in parasite, ionic balance facilitates parasite invasion, augmentation and transmission. Past few decades have witnessed tremendous advancement in understanding the relevance of ionic transit in parasites. Perhaps, not surprisingly, disruption of ionic homeostasis was thought to be detrimental for parasite. Compounds like ionophores are known to facilitate ionic transport across membrane down their electrochemical gradient. Despite continuous effort, malaria treatment is still a challenge particularly due to the development of resistance among parasites against existing therapeutic options. However, repurposing the existing drugs can be advantageous over de novo drug development programs in terms of cost and associated risk factors. Ionophores, being used in coccidiosis have proven to be of significance in the treatment of experimental models of malaria. Several recent reports have highlighted the attractive potential of ionophores such as Monensin, Maduramicin, Valinomycin, etc., that can act against multiple stages of malarial parasite's life cycle. Improved variety of these molecules may help in mitigating the drug resistance problems as well. This review is an attempt to examine the relevant literature and provide insight into the mechanism and prospects of different classes of ionophores as promising anti-malarial potpourri.