Current Status of Malaria Control

Abstract

Malaria caused by Plasmodium parasites kills approximately 1-3 million people and causes disease in 300-500 million people annually throughout the world. The current approaches to curtail this disease include vector control, vaccination, immunotherapy and chemotherapy. The vector control is achieved by reducing vector density, interrupting their life cycle, and creating a barrier between the human host and mosquitoes. A number of vaccine candidates are being clinically tried and R&D effort in this direction is coming in a big way. Currently there are only limited safe drugs for the treatment of this disease, however, reports of emerging resistance against existing drugs warrant the introduction of new drugs, which are unlikely to come from pharmaceutical industries because of limited commercial opportunities. One of the most important current approaches to develop new drugs involves the synthesis of chemical libraries and evaluate them against most validated biochemical targets of malarial parasite. Although a number of such targets in antimalarial drug development are known today, yet only validated and selective biochemical targets including mitochondrial transport, glycolic pathway, folate pathway, proteases and heme metabolism, apicoplast metabolism, glycophospatidyl inositol, lipid metabolism (glycerophospholipids), peptidyl deformylase and oxidative stress in parasite-infected erythrocytes have been discussed here. The well known antimalarial drugs and different drug combinations for the treatment of malaria are also briefly reviewed. A survey of the recently discovered new molecules active against malaria has also been narrated. Lastly, the future of malaria chemotherapy and new directions emerging from literature has been elucidated.

Primaquine revisited six decades after its discovery

“…Both types of PQ modification, i.e., insertion of substituents at the quinoline ring and modification of the terminal primary amino group, gave rise to the discovery of highly promising drugs [199,200]. In this connection, this last section will be devoted to three PQ derivatives that, given their excellent therapeutic prospects, are now under transition to (NPC 1161C, 32) or already in advanced phases of clinical assays (bulaquine or elubaquine, 33; tafenoquine, 34) [160] as anti-malarials, and sitamaquine (35) as a leishmanicidal and anti-Pneumocystis agent.…”

The cyanobacterial genome core and the origin of photosynthesis

“…The proteins of likely cyanobacterial origin that are shared by apicomplexans and other plastid-carrying eukaryotes but that are missing in other eukaryotes include enzymes of the deoxyxylulose pathway of terpenoid biosynthesis, fatty acid biosynthesis, DNA gyrase, peptide deformylase, and several others. Most of these proteins are validated targets for antimalarial drugs (44,45). Other proteins with similar phylogenetic profiles, such as translation initiation factor IF-1 (InfA), phosphoenolpyruvate carboxylase, and several poorly characterized proteins (e.g., seed maturation protein PM23) are also likely to function in apicoplasts and might merit exploration as additional drug targets.…”

Design and Synthesis of Hydroxyferroquine Derivatives with Antimalarial and Antiviral Activities

“…Test procedures for laboratory strains were as previously described (0.5% hematocrit; 0.5% parasitaemia) (4,5). IC 50 were calculated from response curves by linear interpolation.…”

“…2,3 Chemists and biologists have combined their efforts in an attempt to find efficient and affordable drugs for the developing countries. Several approaches have been investigated 4,5 and new projects at various stages of development have emerged. 6 Besides, apart from these classical organic schemes, an atypical strategy based on modification of the old drug chloroquine (CQ) by a ferrocenyl fragment led to the identification of FQ (Figure 1).…”