Plasmodium falciparum

Malaria remains a major public health problem in many parts of the world, including Southeast Asia, sub-Saharan Africa and Latin America where an estimated 300-500 million people are infected. 1-3 million die of malaria every year. The etiologic agents of malaria are protozoan parasites of the genus Plasmodium. Of the four pathogens that can cause malaria in humans (Plasmodium falciparum, P. vivax, P. ovale,... 

Malaria is transmitted from person to person by a certain species of the Anopheles mosquito. The four different protozoans causing malaria are Plasmodium falciparum, P. malariae, P. ovale, and P. vivax. Drugp used to treat or prevent malaria are called anti malarial drags. Three antimalarial drugs are discussed in the chapter chloroquine, doxycycline, and quinine sulfate. Other examples of antimalarial drugs in use today are listed in the Summary Drug Table Antimalarial Drugs. 

Inhibitors for proteases plasmepsin I and II of the malaria parasite Plasmodium falciparum, with a good plasmepsin/human protease cathepsin D selectivity, have been identified via library construction involving rapid microwave-accelerated Suzuki reactions [57]. The phenyl ring of the biphenyl unit in the lead compound M-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-phenyl-benzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methylpropyl)pyridine-2-carboxamide has been altered by performing Suzuki reactions on N-((lS)-l- [((lS,2S)-3- [(lS)-2-amino-l-(4-bromobenzyl)-2-oxoethyl]amino -2-hydroxy-l-phenoxypropyl)amino]carbonyl -2-methyl-propyl)pyridine-2-carboxamide (Scheme 37). In particular, a 2-benzofuryl moiety proved to be interesting since a Ki value of 13 nM for plasmepsin I and... 

Plasmodium falciparum DHFR inhibitor, Ki = 0.9 jxM, Ki vs. different resistant strains = 0.6-2.1 xM... 

Toyoda T, Brobey RKB, Sano G, Horii T, Tomioka N, Itai Akiko. Lead discovery of inhibitors of the dihydrofolate reductase domain of Plasmodium falciparum dihydrofolate reductase-thymidylate synthase. Biochem Biophys Res Commun 1997 235 515-19. 

Rastelli G, Pacchioni S, Sirawaraporn W, Sirawaraporn R, Parenti MD, Ferrari AM. Docking and database screening reveal new classes of Plasmodium falciparum dihydrofolate reductase inhibitors. J Med Chem 2003 46 2834-45. 

Bfx and Fx derivatives have been evaluated against the parasites Trypanosoma cruzi (T. cruzi), which is responsible for American Trypanosomiasis and Plasmodium falciparum (P. falciparum) responsible for Malaria. 

Narum, D. L., Welling, G. W., and Thomas, A. W., Ion-exchange-immuno-affinity purification of a recombinant baculovirus Plasmodium falciparum apical membrane antigen, PF83/AMA-1, /. Chromatogr. A, 657, 357, 1993. 

Malaria is transmitted by the bites of the Anopheles mosquitoes which introduce into the bloodstream one of four species of sporozoites of the plasmodia (Plasmodium falciparum, P. ovale, P. vivax or P. malariae). Initial symptoms of malaria are nonspecific and may resemble influenza and include chills, headache, fatigue, muscle pain, rigors, and nausea. The onset of the symptoms is between 1 to 3 weeks following exposure. Fever may appear 2 to 3 days after initial symptoms and may follow a pattern and occur every 2 or 3 days (P. vivax, P. ovale and P. malariae). Fever with P. falciparum can be erratic and may not follow specific patterns. It is not unusual for patients to have concomitant infections with P. vivax and P. falciparum. Falciparum malaria must always be regarded as a life-threatening medical emergency. 

Gardner, M. J. et al. Genome sequence of the human malaria parasite Plasmodium falciparum. Nature 2002, 419, 498-511. 

Francis, S. Sullivan, D. J. Goldberg, D. E. Hemoglobin metabolism in the malaria parasite Plasmodium falciparum. Annu. Rev. Microbiol. 1997, 51, 97-123. 

Lauer, S. A. Chatterjee, S. Haidar, K. Uptake and hydrolysis of sphingomyelin analogues in Plasmodium falciparum-infected red cells. Mol. Biochem. Parasitol. 2001, 115, 275-281. 

Pessi, G Kociubinski, G. Ben Mamoun, C. A pathway for phosphatidylcholine biosynthesis in Plasmodium falciparum involving phosphoethanolamine methyla-tion. Proc. Nat. Acad. Sci. USA 2004,101, 6206-6211. 

Kain, K.C., Craig, A.A. and Ohrt, C. (1996) Single-strand conformational polymorphism analysis differentiates Plasmodium falciparum treatment failures from re-infections. Molecular and Biochemical Parasitology 79, 167—175. 

The pepsin, activated by cleavage of a proenzyme, has two putative active site domains comprising hydrophobic-hydrophobic-Asp-Thr-Gly amino acids, is potentially glycosylated and has a free cysteine residue which may allow it to form dimers, as in the case of human and Plasmodium falciparum-derived aspartyl proteases (Longbottom et al., 1997). However,... 

Baird et al. [154] reported that primaquine base (30 mg/day) had protective efficacy against Plasmodium falciparum and P. vivax of 85-93%. Among 339... 

Ho CK, Shuman S. A yeast-like mRNA capping apparatus in Plasmodium falciparum. Proc Natl Acad Sci USA 2001 98[6] 3050-3055. 

Gardner M), Tettelin H, Carucci DJ et al. Chromosome 2 sequence of the human malaria parasite Plasmodium falciparum. Science 1998 282[5391] 1126 1132. Hoffman SL, Rogers WO, Carucci DJ, Venter JC. From genomics to vaccines malaria as a model system. Nature Med 1998 4[12] 1351—1353. 

Gowda, A.S.P., Madhunapantula, S.V., Achur, R.N., Valiyaveettil, M., Bhavanandan, V.P., and Gowda, D. C. (2007) Structural basis for the adherence of plasmodium falciparum-infected erythrocytes to chon-droitin 4-sulfate and design of novel photoactivable reagents for the identification of parasite adhesive proteins./. Biol. Chem. 282, 916-928. 

Plasmodium falciparum (PfMSPl) Tobacco leaf Antigenic characteristics identical to E. coli expressed protein. Immunogenic characteristics identical to E. coli expressed protein. 40,106... 

---