Synthesis and biological evaluation of cyclopropyl analogues of fosmidomycin as potent Plasmodium falciparum growth inhibitors

被引：56

作者：

Devreux, V

Wiesner, J

Goeman, JL

Van der Eycken, J

Jomaa, H

Van Calenbergh, S

机构：

[1] Univ Ghent, Fac Sci, Dept Organ Chem, Organ & Bioorgan Chem Lab, B-9000 Ghent, Belgium

[2] Univ Klinikum Giessen, Inst Clin Chem & Pathobiol, D-35392 Giessen, Germany

[3] Univ Klinikum Marburg, Inst Clin Chem & Pathobiol, D-35392 Giessen, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2006年 / 49卷 / 08期

关键词：

D O I：

10.1021/jm051177c

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of fosmidomycin analogues featuring restricted conformational mobility has been synthesized and evaluated as inhibitors of 1-deoxy-D-xylulose 5-phosphate (DOXP) reductoisomerase and as growth inhibitors of P. falciparum. The enantiomerically pure trans-cyclopropyl N-acetyl analogue 3b showed comparable inhibitory activity as fosmidomycin toward E. coli DOXP reductoisomerase and proved equally active when tested in vitro for P. falciparum growth inhibition. Conversely, the alpha-phenyl cis-cyclopropyl analogue 4 showed virtually no inhibition of the enzyme.

引用

收藏

页码：2656 / 2660

页数：5

相关论文

共 22 条

[1] Short-course regimens of artesunate-fosmidomycin in treatment of uncomplicated Plasmodium falciparum malaria [J].

Borrmann, S ;

Adegnika, AA ;

Moussavou, F ;

Oyakhirome, S ;

Esser, G ;

Matsiegui, PB ;

Ramharter, M ;

Lundgren, I ;

Kombila, M ;

Issifou, S ;

Hutchinson, D ;

Wiesner, J ;

Jomaa, H ;

Kremsner, PG .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2005, 49 (09) :3749-3754

[2] Fosmidomycin-clindamycin for the treatment of Plasmodium falciparum malaria [J].

Borrmann, S ;

Issifou, S ;

Esser, G ;

Adegnika, AA ;

Ramharter, M ;

Matsiegui, PB ;

Oyakhirome, S ;

Mawili-Mboumba, DP ;

Missinou, MA ;

Kun, JFJ ;

Jomaa, H ;

Kremsner, PG .

JOURNAL OF INFECTIOUS DISEASES, 2004, 190 (09) :1534-1540

[3] Fosmidomycin-clindamycin for plasmodium falciparum infections in African children [J].

Borrmann, S ;

Adegnika, AA ;

Matsiegui, PB ;

Issifou, S ;

Schindler, A ;

Mawili-Mboumba, DP ;

Baranek, T ;

Wiesner, J ;

Jomaa, H ;

Kremsner, PG .

JOURNAL OF INFECTIOUS DISEASES, 2004, 189 (05) :901-908

[4] Synthesis and biological evaluation with plant cells of new fosmidomycin analogues containing a benzoxazolone or oxazolopyridinone ring [J].

Courtois, M ;

Mincheva, Z ;

Andreu, F ;

Rideau, M ;

Viaud-Massuard, MC .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2004, 19 (06) :559-565

[5] The stereoselective synthesis of cyclopropylphosphonate analogs of nucleotides [J].

Hah, JH ;

Gil, JM ;

Oh, DY .

TETRAHEDRON LETTERS, 1999, 40 (47) :8235-8238

[6] Inhibitors of the nonmevalonate pathway of isoprenoid biosynthesis as antimalarial drugs [J].

Jomaa, H ;

Wiesner, J ;

Sanderbrand, S ;

Altincicek, B ;

Weidemeyer, C ;

Hintz, M ;

Türbachova, I ;

Eberl, M ;

Zeidler, J ;

Lichtenthaler, HK ;

Soldati, D ;

Beck, E .

SCIENCE, 1999, 285 (5433) :1573-1576

[7] Alkali metal alkoxide clusters:: Convenient catalysts for the synthesis of methylphosphonates [J].

Kissling, RM ;

Gagné, MR .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (05) :1585-1590

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

Kuntz, L ;

Tritsch, D ;

Grosdemange-Billiard, C ;

Hemmerlin, A ;

Willem, A ;

Bacht, TJ ;

Rohmer, M .

BIOCHEMICAL JOURNAL, 2005, 386 :127-135

[9]

Kurz T, 2003, Z NATURFORSCH B, V58, P457

[10] Fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose 5-phosphate reductoisomerase in the nonmevalonate pathway for terpenoid biosynthesis [J].

Kuzuyama, T ;

Shimizu, T ;

Takahashi, S ;

Seto, H .

TETRAHEDRON LETTERS, 1998, 39 (43) :7913-7916