Isoprenoid Biosynthesis of the Apicoplast as Drug Target

Author(s): Jochen Wiesner, Hassan Jomaa.

Journal Name: Current Drug Targets

Volume 8 , Issue 1 , 2007

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.

Keywords: Malaria, apicoplast, isoprenoid biosynthesis, DOXP reductoisomerase, fosmidomycin, FR900098

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Article Details

VOLUME: 8
ISSUE: 1
Year: 2007
Page: [3 - 13]
Pages: 11
DOI: 10.2174/138945007779315551

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