Enzymes of Isoprenoid Biosynthesis and Control of Malarial Parasite Plasmodium falciparum

There is high importance for the control of parasite Plasmodium falciparum which is responsible for causing malaria. Following the classical mevalonate pathway, the metabolite methylerythritol phosphate (MEP) is responsible for biosynthesis of isoprenoids, which is a desirable therapeutic target in the form of biological molecules, pathways, and physiological responses to treat malaria. The isoprenoid is active in Plasmodium apicoplast, and its byproducts are transferred to the cytoplasm where they take part in the production of glycoproteins, the electron transport chain and a parallel tRNA structural modification, and a number of other physiological and biological activities. Fosmidomycin targets the IspC enzyme (DXP reductoisomerase), which is the first step in the biosynthetic pathway for isopentenyl diphosphate that does not involve the mevalonate pathway. Additionally, MMV008138 targets the IspD enzyme. Both enzymes have demonstrated significant antimalarial effectiveness in cultures of the parasite P. falciparum. Both drugs have been evaluated for enzymes playing active role in controlling P. falciparum. The applications of fosmidomycin against P. falciparum are currently restricted by its weaker cellular absorption, comparatively shorter half-life, and higher toxicity at higher dosages. Several enzymes in the pathway’s potential as potential therapeutic targets have also been identified. In this chapter, Plasmodium is highlighted more than other pharmacological compounds that have been tried against these targets. Literature and research results from diverse studies conducted confirm that the MEP route in Plasmodium apicoplasts is a prominent therapeutic target, particularly during erythrocytic phases. Therefore, before evaluating any novel compound as a strong antimalarial, the key bottlenecks, bioavailability, and toxicity must be solved.