Plasmodium falciparum, inhibition

Chen M, Theander TG Christensen SB, Hviid L, Zhai L, Kharazmi A. (1994) Licochalcone A, a new antimalarial agent, inhibits in vitro growth of the human malaria parasite Plasmodium falciparum and protects mice from P. yoelii mitctxon. Antimicrob Agents Chemother 38 1470-1475. 

Iron(n) is known to decompose hydrogen and dialkyl peroxides to free radicals by reductive cleavage of the 0—0 bond and early investigations established the parasite s sensitivity to these species. When treated with radiolabelled C-artemisinin, the hemin-hemozoin fraction of the lysed malaria-infected erythrocytes was shown to contain a radiolabel, though the mechanism of incorporation is not clear. Meshnick and coworkers demonstrated that uninfected cells did not contain radiolabelled proteins whereas six radiolabelled proteins were isolated from cells infected with the Plasmodium falciparum (P. falciparum) strain of the parasite. It was suspected that one of the alkylated proteins was the Histidine Rich Protein (HRP) that was known to bind multiple heme monomers and therefore thought to be instrumental to the parasite s detoxification process. Moreover, iron chelators were found to inhibit the lethal effects of peroxides on the parasite. ... 

Mecfianism of Action An antimalarial and antirheumatic that eliminates tissue exo-erythrocytic forms of Plasmodium falciparum. Disrupts mitochondria and binds to DNA. Therapeutic Effect Inhibits parasite growth. 

It has been established that DXS catalyzes the first step in a novel biosynthetic pathway leading to isoprenoids in bacteria, algae, plant chloroplasts, and in the malaria parasite, Plasmodium falciparum. DXS is therefore a novel target for antibiotics, herbicides, or anti-malarials. Our work has contributed to an understanding of the novel biosynthetic pathway and could further open new perspectives on how to inhibit the pathway in pathogenic bacteria, protists, or weeds. 

Nirmalan, N., Sims, P.F.C. and Hyde, J.E. (2004) Quantitative proteomics of the human malaria parasite Plasmodium falciparum and its application to studies of development and inhibition. Molecular Microbiology 52, 11 87-11 99. 

McRobert, L. and McConkey, C.A. (2002) RNA interference (RNAi) inhibits growth of Plasmodium falciparum. Molecular and Biochemical Parasitology 11 9, 273-278. 

N. C. A three-dimensional in silico pharmacophore model for inhibition of Plasmodium falciparum cyclic-dependent kinases and discovery of different classes... 

A rapid semiautomated microdilution method for the microbiological assay of the chloroquine has been developed by Desgardins (26). Antimalarial activity of chloroquine may be studied against cultured Plasmodium falciparum, microplates are used to prepare serial dilution of the drug. Parasites obtained from continuous stock cultures are subcultured in the micro-plates for 42 h. Inhibition of uptake of a radio labeled nucleic acid precursor by parasites serves as the indicator of antimicrobial activity. 

Choubey V, Maity P, Guha M et al (2007) Inhibition of Plasmodium falciparum choline kinase by hexadecyltrimethylammonium bromide a possible antimalarial mechanism. Antimicrob Agents Chemother 51(2) 696-706... 

Caridha D, Kathcart AK, Jirage D, Waters NC (2010) Activity of substituted thiophene sulfonamides against malarial and mammalian cyclin dependent protein kinases. Bioorg Med Chem Lett 20(13) 3863-3867 Geyer JA, Keenan SM, Woodard CL et al (2009) Selective inhibition of Pfinrk, a Plasmodium falciparum CDK, by antimalarial l,3-diaryl-2-propenones. Bioorg Med Chem Lett 19(7) 1982-1985 Jirage D, Chen Y, Caridha D et al (2010) The malarial CDK Pfinrk and its effector PfMATl phosphorylate DNA replication proteins and co-localize in the nucleus. Mol Biochem Parasitol 172(1) 9-18... 

Scientists at the University of Michigan Medical School, in collaboration with those at the Indian Institute of Science in Bangalore, have carried out tests on curcumin that show it to inhibit the drug-resist-ant forms of malaria and reported their findings in the Journal of Biological Chemistry in December 2004. Mice infected with the related parasite, Plasmodium falciparum, which causes rodent malaria, were fed curcumin and this reduced the number of parasites in the blood by as much as 90%, and completely protected more than a quarter of mice to whom it was given. Whether it could be a treatment for human malarial infection remains to be seen. 

Queen SA, Jagt DL, Reyes P (1990) In vitro susceptibilities of Plasmodium falciparum to compounds which inhibit nucleotide metabolism. Antimicrob Agents Chemother. 34 1393—1398... 

Heath HT, Bailey BN, Kendrick H, Yardley V, Caldera A, Lira R, Urbina JA, Moreno SNJ, Docampo R Croft SL, Oldfield E. Bisphosphonates inhibit the growth of Trypanosoma brucei, Trypanosoma cruzi, Leishmania donovani, Toxoplasma gondii, and Plasmodium falciparum a potential route to chemotherapy. J. Med. Chem., 2001, 44, 909-916. 

Artemisinin (quinghaosu) (3,12-peroxyC60 ] C50L ( C6 ) from Artemisia annua (Asteraceae) is of major importance as an antimalarial because of extensive resistance of Plasmodium falciparum to antimalarials such as chloroquine. Artemisinin in has a 3,12-peroxy (-0—0—) substituent spanning the C60 ring. Artemisinin alkylates and inhibits glutathione S-transferase. 

---