Isoprenoid biosynthesis as a target for antibacterial and antiparasitic drugs: phosphonohydroxamic acids as inhibitors of deoxyxylulose phosphate reducto-isomerase

被引:89
作者
Kuntz, L
Tritsch, D
Grosdemange-Billiard, C
Hemmerlin, A
Willem, A
Bacht, TJ
Rohmer, M
机构
[1] Univ Strasbourg, Inst Le Bel, CNRS, UMR 7123, F-67070 Strasbourg, France
[2] Inst Biol Mol Plantes, CNRS, UPR 2357, F-67083 Strasbourg, France
关键词
antibacterial drug; 1-deoxy-D-xylulose; 5-phosphate; 1-deoxy-D-Xylulose 5-phosphate reducto-isomerase; isoprenoid biosynthesis; malaria; 2-C-methyl-D-erythritol; 4-phosphate;
D O I
10.1042/BJ20041378
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Isoprenoid biosynthesis via the methylerythritol phosphate pathway is a target against pathogenic bacteria and the malaria parasite Plasniodium falciparum. 4-(Hydroxyamino)-4-oxobutyl-phosphonic acid and 4-[hydroxy(methyl)amino]-4-oxobutyl phosphonic acid, two novel inhibitors of DXR (1-deoxy-D-xylulose 5-phosphate reducto-isomerase), the second enzyme of the pathway, have been synthesized and compared with fosmidomycin, the best known inhibitor of this enzyme. The latter phosphonohydroxamic acid showed a high inhibitory activity towards DXR, much like fosmidomycin, as well as significant antibacterial activity against Escherichia coli in tests on Petri dishes.
引用
收藏
页码:127 / 135
页数:9
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