Publication Date:
2002-02-16
Description:
During asexual development within erythrocytes, malaria parasites synthesize considerable amounts of membrane. This activity provides an attractive target for chemotherapy because it is absent from mature erythrocytes. We found that compounds that inhibit phosphatidylcholine biosynthesis de novo from choline were potent antimalarial drugs. The lead compound, G25, potently inhibited in vitro growth of the human malaria parasites Plasmodium falciparum and P. vivax and was 1000-fold less toxic to mammalian cell lines. A radioactive derivative specifically accumulated in infected erythrocytes to levels several hundredfold higher than in the surrounding medium, and very low dose G25 therapy completely cured monkeys infected with P. falciparum and P. cynomolgi.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Wengelnik, Kai -- Vidal, Valerie -- Ancelin, Marie L -- Cathiard, Anne-Marie -- Morgat, Jean Louis -- Kocken, Clemens H -- Calas, Michele -- Herrera, Socrates -- Thomas, Alan W -- Vial, Henri J -- New York, N.Y. -- Science. 2002 Feb 15;295(5558):1311-4.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉CNRS UMR 5539, CP 107, CNRS UMR 5810, CP 22, Universite Montpellier II, Place E. Bataillon, 34095 Montpellier Cedex 5, France.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/11847346" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antimalarials/administration & dosage/*pharmacokinetics/*pharmacology/therapeutic
;
use
;
Aotus trivirgatus
;
Cell Line
;
Cell Survival/drug effects
;
Dose-Response Relationship, Drug
;
Erythrocytes/metabolism/*parasitology
;
Humans
;
Macaca mulatta
;
Malaria/*drug therapy/parasitology
;
Malaria, Falciparum/drug therapy/parasitology
;
Malaria, Vivax/drug therapy/parasitology
;
Membrane Transport Modulators
;
Membrane Transport Proteins/antagonists & inhibitors
;
Parasitemia/drug therapy
;
Phosphatidylcholines/biosynthesis
;
Plasmodium/*drug effects
;
Plasmodium cynomolgi/drug effects
;
Plasmodium falciparum/drug effects
;
Plasmodium vivax/drug effects
;
Pyrrolidines/administration & dosage/*pharmacokinetics/*pharmacology/therapeutic
;
use
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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