| Abstract | In Plasmodium falciparum the biosynthesis of isoprenoids is achieved by the mevalonate-independent 1-deoxy-d-xylulose 5-phosphate (DOXP) pathway. The enzymes of the DOXP pathway are localised inside the plastid-like organelle (apicoplast). Fosmidomycin inhibits DOXP reductoisomerase, the second enzyme of this pathway. The antimalarial activity of fosmidomycin was established in vitro and in a rodent malaria model. Fosmidomycin alone or in combination with clindamycin was evaluated for the treatment of acute uncomplicated P. falciparum malaria in early phase II studies. Fosmidomycin monotherapy led to a fast parasite and fever clearance but was inefficient in radical elimination of the parasites. With the fosmidomycin-clindamycin combinations the cure ratio on day 28 was 100 % (10/10) with treatment durations of 5 and 4 days. The cure ratio was 90 % (9/10) with treatment duration of 3 days. |
| Authors | Jochen Wiesner, Hassan Jomaa
(Affiliation: Universitätsklinikum Giessen und Marburg, Institut für Klinische Chemie und Pathobiochemie, Gaffkystrasse 11, 35392 Giessen, Germany.)
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| Journal | Current drug targets
(Curr Drug Targets)
Vol. 8
Issue 1
Pg. 3-13
(Jan 2007)
ISSN: 1873-5592 Netherlands |
| PMID | 17266527
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
|
| Chemical References |
|
| Topics |
- Animals
- Drug Delivery Systems
(methods)
- Humans
- Malaria, Falciparum
(drug therapy)
- Organelles
(metabolism)
- Plasmodium falciparum
(drug effects, metabolism)
- Terpenes
(metabolism)
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