Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs.
Science
; 285(5433): 1573-6, 1999 Sep 03.
Article
em En
| MEDLINE
| ID: mdl-10477522
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.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases
/
Pentosefosfatos
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Plasmodium falciparum
/
Terpenos
/
Aldose-Cetose Isomerases
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Hemiterpenos
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Fosfomicina
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Malária
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Complexos Multienzimáticos
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Antimaláricos
Limite:
Animals
Idioma:
En
Revista:
Science
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Alemanha