gms | German Medical Science

11th Malaria Meeting

Malaria Group / Section Antiparasitic Chemotherapy of the Paul-Ehrlich-Society (PEG e. V.) in cooperation with the German Society for Tropical Medicine and International Health (DTG e. V.) and the German Society for Parasitology (DGP e. V.)

08.11. - 09.11.2013, Aachen

Isoprenoid biosynthesis as target for new antimalarial drugs

Meeting Abstract

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  • Jochen Wiesner - Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Project Group Bioresources, Gießen, Germany

11th Malaria Meeting. Aachen, 08.-09.11.2013. Düsseldorf: German Medical Science GMS Publishing House; 2014. Doc13mal06

doi: 10.3205/13mal06, urn:nbn:de:0183-13mal063

Published: January 29, 2014

© 2014 Wiesner.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( You are free: to Share – to copy, distribute and transmit the work, provided the original author and source are credited.



The biosynthesis of isoprenoids is achieved in P. falciparum via the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway, which is typically used by plastids of plants and by most bacteria. In P. falciparum the enzymes of the DXP pathway are localized inside the plastid-like organelle (apicoplast). Fosmidomycin (FR-31564), an antimicrobial compound originally isolated from the culture broth of Streptomyces lavendulae, as well as some related compounds are highly specific inhibitors of DXP reductoisomerase. A total of 9 clinical phase II studies on the efficacy of fosmidomycin for the treatment of P. falciparum malaria have been conducted. Fosmidomycin monotherapy resulted in fast parasite and fever clearance but was inefficient to eliminate the parasites completely. Higher efficacy was achieved by combining fosmidomycin with clindamydin, which had been shown in vitro to act synergistically. A combination of fosmidomycin (30 mg/kg) and clindamycin (10 mg/kg) administered orally twice daily for 3 days resulted in a cure rate of approximately 90% in patients older than 3 years. The fosmidomycin derivative FR-900098, which can be isolated from the culture broth of S. rubellomurinus or produced synthetically, exhibits low toxicity and approximately 2-fold improved antimalarial activity, thus representing a promising new development candidate.