Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs

被引：948
|
作者：
Jomaa, H
Wiesner, J
Sanderbrand, S
Altincicek, B
Weidemeyer, C
Hintz, M
Türbachova, I
Eberl, M
Zeidler, J
Lichtenthaler, HK
Soldati, D
Beck, E
机构：
[1] Univ Giessen, Acad Hosp Ctr, Inst Biochem, D-35392 Giessen, Germany
[2] Zentrum Mol Biol, D-69120 Heidelberg, Germany
[3] Univ Karlsruhe, Inst Bot 1, D-76128 Karlsruhe, Germany
来源：
SCIENCE | 1999年 / 285卷 / 5433期
关键词：
D O I：
10.1126/science.285.5433.1573
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
引用
收藏
页码：1573 / 1576
页数：4
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