title: Isoprenoid biosynthesis of the apicoplast as drug target.
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.affiliation: Universitätsklinikum Giessen und Marburg, Institut für Klinische Chemie und Pathobiochemie, Gaffkystrasse 11, 35392 Giessen, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Wiesner
authors.forename: Hassan
authors.initials: H
authors.lastname: Jomaa
mesh_terms: D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D016778:Malaria, Falciparum / Q000188:drug therapy; D015388:Organelles / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects / Q000378:metabolism*; D013729:Terpenes / Q000378:metabolism*
chemical_list: D013729:Terpenes