Fosmidomycin for the treatment of malaria

被引：100

作者：

Wiesner, J

Borrmann, S

Jomaa, H

机构：

[1] Jomaa Pharmaka GmbH, D-35392 Giessen, Germany

[2] Univ Tubingen, Inst Trop Med, Dept Parasitol, D-72074 Tubingen, Germany

来源：

PARASITOLOGY RESEARCH | 2003年 / 90卷 / Suppl 2期

关键词：

D O I：

10.1007/s00436-002-0770-9

中图分类号：

R38 [医学寄生虫学]; Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ; 100103 ;

摘要：

In malaria parasites, isoprenoids are synthesised by the mevalonate independent 1-deoxy-D-xyluose 5-phosphate (DOXP) pathway. Fosmidomycin, a natural antibiotic originally developed for the treatment of bacterial infections, represents an inhibitor of DOXP reductoisomerase, an essential enzyme of this pathway. In recent clinical studies it was shown that fosmidomycin is effective in curing uncomplicated Plasmodium falciparum malaria in humans. The treatment was well tolerated and resulted in a fast parasite and fever clearance. However, the high rate of recrudescence precludes the use of fosmidomycin as a monotherapy. In drug combination studies, synergy of fosmidomycin with clindamycin was observed. Clinical studies with a fosmidomycin-clindamycin combination are currently ongoing.

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页码：S71 / S76

页数：6

相关论文

共 40 条

[1] LytB, a novel gene of the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli [J].

Altincicek, B ;

Kollas, AK ;

Eberl, M ;

Wiesner, J ;

Sanderbrand, S ;

Hintz, M ;

Beck, E ;

Jomma, H .

FEBS LETTERS, 2001, 499 (1-2) :37-40

[2] GcpE is involved in the 2-C-methyl-D-erythritol 4-phosphate pathway of isoprenoid biosynthesis in Escherichia coli [J].

Altincicek, B ;

Kollas, AK ;

Sanderbrand, S ;

Wiesner, J ;

Hintz, M ;

Beck, E ;

Jomaa, H .

JOURNAL OF BACTERIOLOGY, 2001, 183 (08) :2411-2416

[3]

[Anonymous], [No title captured]

[4] BIOCHEMISTRY OF POLYISOPRENOID BIOSYNTHESIS [J].

BEYTIA, ED ;

PORTER, JW .

ANNUAL REVIEW OF BIOCHEMISTRY, 1976, 45 :113-142

[5] Protein prenyl transferase activities of Plasmodium falciparum [J].

Chakrabarti, D ;

Azam, T ;

DelVecchio, C ;

Qiu, LB ;

Park, Y ;

Allen, CM .

MOLECULAR AND BIOCHEMICAL PARASITOLOGY, 1998, 94 (02) :175-184

[6] Active isoprenoid pathway in the intra-erythrocytic stages of Plasmodium falciparum:: presence of dolichols of 11 and 12 isoprene units [J].

Couto, AS ;

Kimura, EA ;

Peres, VJ ;

Uhrig, ML ;

Katzin, AM .

BIOCHEMICAL JOURNAL, 1999, 341 :629-637

[7]

de Macedo CS, 2002, FEMS MICROBIOL LETT, V207, P13, DOI 10.1111/j.1574-6968.2002.tb11021.x

[8] Distribution of the mevalonate and glyceraldehyde phosphate/pyruvate pathways for isoprenoid biosynthesis in unicellular algae and the cyanobacterium Synechocystis PCC 6714 [J].

Disch, A ;

Schwender, J ;

Müller, C ;

Lichtenthaler, HK ;

Rohmer, M .

BIOCHEMICAL JOURNAL, 1998, 333 :381-388

[9] Enzymology, structure, and dynamics of acetohydroxy acid isomeroreductase [J].

Dumas, R ;

Biou, V ;

Halgand, F ;

Douce, R ;

Duggleby, RG .

ACCOUNTS OF CHEMICAL RESEARCH, 2001, 34 (05) :399-408

[10] A plastid organelle as a drug target in apicomplexan parasites [J].

Fichera, ME ;

Roos, DS .

NATURE, 1997, 390 (6658) :407-409

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