Road towards development of new antimalarial: organelle associated metabolic pathways in Plasmodium as drug targets and discovery of lead drug candidates

Malaria remains a global threat with millions of deaths annually. Emergence of parasite strains resistant to widely used antimalarials, including the artemisinin combination therapy (ACT), and the absence of an effective vaccine makes treatment of malaria difficult than ever before. The need of the hour is to re-evaluate the chemotherapeutic approach and to identify new drug targets and develop new pharmacophores against the parasite. An important approach for antimalarial drug discovery is to understand critical metabolic pathways in the parasite which may help us to identify critical targets in the parasites and design specific inhibitors for these targets. Here, we have discussed proteins and pathways in different parasite organelles, i.e. apicoplast, mitochondrial and food vacuole, which have been suggested as potential drug targets; these unique parasite proteins can be targeted to develop new and novel antimalarials. In addition, we have also discussed several antimalarial projects currently under different stages of drug development pipeline. These promising antimalarial compounds have the potential to overcome multidrug resistance. Ongoing global efforts to develop new antimalarials and to identify drug targets suggest a promising future on malaria elimination and eradication