Scaffold hopping to percept the achiral compound and functionalizing on target protein plasmepsin II

Abstract

Malaria is a vector-borne disease caused by protozoan parasites of the genus Plasmodium i.e. Plasmodium vivax, Plasmodium ovale, Plasmodium falciparum and Plasmodium malariae. Only these four types of the plasmodium parasite can infect humans as partial prophylaxis infection; the most serious form of disease caused by Plasmodium falciparum. During infection, Plasmodium merozoites invade and then replicate within red blood cells. During the log phase within the host cell, the parasite obtains nutrients by taking up and then digesting hemoglobin within an acidic food vacuole. The digestion of hemoglobin releases monomeric α-hematin (ferriprotoporphyrin IX). Released compound predicting its hypertoxicity property, since it is a pro-oxidant and it catalyzes the production of reactive oxygen species. Oxidative stress is believed to be generated during the conversion of heme to hematin.1 Free hematin can also bind and then the disrupt cell membranes, damaging cell structures and causing the lysis of the host erythrocyte. Reporting a novel mechanism that the host utilizing Toll-like receptor (TLR) 9 to recognize Plasmodium DNA, which may be a prior induction of fever during the replicative, process (Lag Phase) disease. These findings reveal an important mechanism of disease patho-physiology that may also apply to other microbial diseases.2 It also corrects previous findings claiming that hemozoin is a direct TLR9 stimulus and refines them by showing that hemozoin itself important for presenting the DNA to TLR9 but does not stimulate the receptive process (Figure 1). Although it is too early to predict how these findings will influence the development of future malaria treatment options, it is likely that it will open new pathways of interference with the malaria fever reaction, and this may influence the course of disease.3,4 Figure 1 Illustrates the potential mechanism of malaria-induced fever, shows that hemozoin contains plasmodial DNA and that it “presents” or internalizes DNA. Plasmodial DNA then intracellularly interacts with TLR9, initiating signal transduction.