Targeting Plasmodium Metabolism to Improve Antimalarial Drug Design

Abstract

Malaria is one of the main infectious diseases in tropical developing countries and represents high morbidity and mortality rates nowadays. The principal etiological agent P. falciparum is transmitted through the bite of the female Anopheles mosquito. The issue has escalated due to the emergence of resistant strains to most of the antimalarials used for the treatment including Chloroquine, Sulfadoxine-Pyrimethamine, and recently Artemisinin derivatives, which has led to diminished effectiveness and by consequence increased the severity of epidemic outbreaks. Due to the lack of effective compounds to treat these drug-resistant strains, the discovery or development of novel anti-malaria drugs is important. In this context, one strategy has been to find inhibitors of enzymes, which play an important role for parasite survival. Today, promising results have been obtained in this regard, involving the entire P. falciparum metabolism. These inhibitors could serve as leads in the search of a new chemotherapy against malaria. This review focuses on the achievements in recent years with regard to inhibition of enzymes used as targets for drug design against malaria.

Over‐expression of DXS gene enhances terpenoidal secondary metabolite accumulation in rose‐scented geranium and Withania somnifera: active involvement of plastid isoprenogenic pathway in their biosynthesis

“…MEP pathway or MVA independent pathway, alternatively known as 1‐deoxy‐ d ‐xylulose‐5‐phosphate pathway operates in plastids, bacteria, green algae and in certain parasites (Lange et al , Hunter ). Therefore, recent studies explore MEP pathway as the target for development of new drugs (Rohdich et al , Avitia‐Domínguez et al ). For production of IPP and DMAPP moiety, MEP pathway proceeds through eight enzymatic reactions in which the first and regulatory step is catalyzed by 1‐deoxy‐ d ‐xylulose‐5‐phosphate synthase ( DXS ) which uses glyceraldehyde‐3‐phosphate (G3P) and pyruvate as a substrate to produce 1‐deoxy‐ d ‐xylulose‐5‐phosphate (Fig.…”