The erythrocytic phase is the most important phase in the life cycle of the parasite, when it invades the RBCs of the

host and forms an acidic compartment in the lysosome known as the digestive vacuole (DV). The parasite grows in the RBCs and feeds on the hemoglobin Thiazovivin cost of the host cytosol. The parasite accumulates the hemoglobin in the DV and degrades it into its component peptides and heme to form a crystalline polymer hemozoin. Chloroquine works on the fact that the uncharged chloroquine species enters the DV and binds to the hematin, thus preventing its addition into the hemozoin formation. Hematin is a toxic byproduct released during proteolysis of hemoglobin which hinders the detoxification process of the parasite. However, in a chloroquine-resistant strain, mutations in a chloroquine transporter protein do not allow the exit of positively charged chloroquine from the vacuole, thus BAY 80-6946 cost resulting in a net decrease in chloroquine levels inside the DV [21]. The mechanism this website by which AMPs LR14 show anti-plasmodial activity on asexual

erythrocytic stages is unclear. However, it can be hypothesized that differences in the membrane composition, i.e., interaction of the positively charged peptides with the negatively charged surface molecules of the parasites, might play a significant role in killing of the host cells. Also, changes in the functional and structural characteristics of infected erythrocytes has also been reported by various workers GNAT2 when the plasmodium-infected cells are targeted with cationic peptides [6]. These modifications include a marked increase in erythrocyte membrane fluidity, alteration of the host cell’s lipid, fatty acid, protein composition, and phospholipid

distribution, and increased membrane permeability. These modifications result in the formation of erythrocyte membrane channels called “new permeability pathways” (NPPs), thus allowing the selective entry of low molecular weight molecules to the infected erythrocytes [22, 23]. In contrast, uninfected erythrocyte membranes retain asymmetry, and phosphatidylserine is not presented at the external surface prior to a pathological stimulus [6, 24, 25]. AMPs may also have an indirect effect on malaria parasite survival. For example, some synthetic peptides have been shown to kill intracellular blood-stage forms of the malaria parasite [26], whereas some studies have shown that AMPs can induce cells to undergo apoptosis [27]. Generally speaking, the positively charged AMPs LR14 are expected to interact electrostatically with the altered and negatively charged plasma membrane of the infected erythrocytes, traversing the membrane of the host and the parasite to reach its target.