Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs-Reference-Cited by-同舟云学术

Inhibitors of the Nonmevalonate Pathway of Isoprenoid Biosynthesis as Antimalarial Drugs

Published:1999-09-03 Issue:5433 Volume:285 Page:1573-1576
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Jomaa Hassan¹,Wiesner Jochen¹,Sanderbrand Silke¹,Altincicek Boran¹,Weidemeyer Claus¹,Hintz Martin¹,Türbachova Ivana²,Eberl Matthias¹,Zeidler Johannes³,Lichtenthaler Hartmut K.³,Soldati Dominique²,Beck Ewald¹

Affiliation:

1. Institute of Biochemistry, Academic Hospital Centre, Justus-Liebig-University, Friedrichstrasse 24, D-35392 Giessen, Germany.

2. Zentrum für Molekulare Biologie, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany.

3. Botanisches Institut II, University of Karlsruhe, Kaiserstrasse 12, D-76128 Karlsruhe, Germany.

Abstract

A mevalonate-independent pathway of isoprenoid biosynthesis present in Plasmodium falciparum was shown to represent an effective target for chemotherapy of malaria. This pathway includes 1-deoxy- d -xylulose 5-phosphate (DOXP) as a key metabolite. The presence of two genes encoding the enzymes DOXP synthase and DOXP reductoisomerase suggests that isoprenoid biosynthesis in P. falciparum depends on the DOXP pathway. This pathway is probably located in the apicoplast. The recombinant P. falciparum DOXP reductoisomerase was inhibited by fosmidomycin and its derivative, FR-900098. Both drugs suppressed the in vitro growth of multidrug-resistant P. falciparum strains. After therapy with these drugs, mice infected with the rodent malaria parasite P. vinckei were cured.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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