Plasmodium falciparum: Transporter and Drug Target

Malaria will continue to be a concern for public health well into the future, as it is responsible for more than 50 million fatalities annually across the globe. In spite of persistent efforts by a large number of countries and substantial investments, the eradication of malaria has proven to be difficult. This is primarily due to the emergence of multidrug resistance against a variety of conventional medications, including artemisinin, which is the most effective antimalarial compound currently available on the market worldwide. In light of this, it is critically necessary to discover and develop novel medications and chemicals that have innovative modes of action and higher levels of efficacy. In this context, the investigation and analysis of transport proteins is one of the most promising disciplines with reference to the reduction of multidrug resistance. Transporters are responsible for mediating the uptake of solutes that target transporters in order to rid the cell of the parasite. This helps to control the growth and survival of intracellular parasites. In this chapter, we focused on the study that was done on inhibitors that block red blood cell transporters and worked as prospective biological targets for an infection caused by Plasmodium falciparum. Anaerobic glycolysis is the source of the energy molecules that are extracted by malaria parasites from red blood cells. To gain access to the ample glucose supply that is present in an infected host, the RBC glucose transporter-1, often known as GLUT-1, along with a hexose transporter, or HT, is utilized. In order to prevent the plasmodium from being clogged, the glucose metabolism produces two lactate anions and two protons as waste, both of which are promptly expelled from the plasmodium. In addition, the missing Plasmodium lactate/H+ co-transporter has been recently discovered as a member of the FNT family of formate–nitrite transporters. This family of formate–nitrite transporters is only found in microbes. The screening of a library of antimalarial compounds with unidentified targets led to the discovery of the FNT-inhibitors known as pentafluoro-3-hydroxy-pent-2-en-1-ones. These inhibitors are highly selective and have a high level of activity. The scientific community is still debating whether or not novel classes of antimalarial drugs should be developed, as well as their modes of binding and sites of action, their mechanisms of action, ways to avoid a putative resistance mutation of the FNT target protein, and whether or not these drugs are appropriate for in vivo research using animal malaria models.