Enzymes of parasite thiol metabolism as drug targets

被引:111
作者
Krauth-Siegel, RL [1 ]
Coombs, GH
机构
[1] Univ Heidelberg, Zentrum Biochem, D-69120 Heidelberg, Germany
[2] Univ Glasgow, Div Infect & Immun, Glasgow G12 8QQ, Lanark, Scotland
来源
PARASITOLOGY TODAY | 1999年 / 15卷 / 10期
关键词
D O I
10.1016/S0169-4758(99)01516-1
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
The potential for chemotherapeutic exploitation of thiol metabolism in parasitic protozoa is reviewed here by Luise Krauth-Siegel and Graham Coombs. The review is based largely on discussions held at a meeting of the COST B9 Action entitled 'Chemotherapy of Protozoal Infections'*. The major questions posed were: which enzymes are the best to target; what further information is required to allow their use for rational drug development; and how can this be achieved most efficiently? Not surprisingly, only partial answers could be obtained in many cases, but the interactive discussion between the multidisciplinary group of participants provided thought-provoking ideas and will help direct future research.
引用
收藏
页码:404 / 409
页数:6
相关论文
共 51 条
[1]   The mechanism of thioredoxin reductase from human placenta is similar to the mechanisms of lipoamide dehydrogenase and glutathione reductase and is distinct from the mechanism of thioredoxin reductase from Escherichia coli [J].
Arscott, LD ;
Gromer, S ;
Schirmer, RH ;
Becker, K ;
Williams, CH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (08) :3621-3626
[2]   The malaria parasite supplies glutathione to its host cell -: Investigation of glutathione transport and metabolism in human erythrocytes infected with Plasmodium falciparum [J].
Atamna, H ;
Ginsburg, H .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1997, 250 (03) :670-679
[3]   Plasmodium falciparum glutathione metabolism and growth are independent of glutathione system of host erythrocyte [J].
Ayi, K ;
Cappadoro, M ;
Branca, M ;
Turrini, F ;
Arese, P .
FEBS LETTERS, 1998, 424 (03) :257-261
[4]   SUBSTRATE INTERACTIONS BETWEEN TRYPANOTHIONE REDUCTASE AND N(1)-GLUTATHIONYLSPERMIDINE DISULFIDE AT 0.28-NM RESOLUTION [J].
BAILEY, S ;
SMITH, K ;
FAIRLAMB, AH ;
HUNTER, WN .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1993, 213 (01) :67-75
[5]   Recent advances in identifying and validating drug targets in trypanosomes and leishmanias [J].
Barrett, MP ;
Mottram, JC ;
Coombs, GH .
TRENDS IN MICROBIOLOGY, 1999, 7 (02) :82-88
[6]   RATIONALLY DESIGNED SELECTIVE INHIBITORS OF TRYPANOTHIONE REDUCTASE - PHENOTHIAZINES AND RELATED TRICYCLICS AS LEAD STRUCTURES [J].
BENSON, TJ ;
MCKIE, JH ;
GARFORTH, J ;
BORGES, A ;
FAIRLAMB, AH ;
DOUGLAS, KT .
BIOCHEMICAL JOURNAL, 1992, 286 :9-11
[7]  
BLUMENSTIEL K, IN PRESS BIOCH PHARM
[8]   Crystal structure of Trypanosoma cruzi trypanothione reductase in complex with trypanothione, and the structure-based discovery of new natural product inhibitors [J].
Bond, CS ;
Zhang, YH ;
Berriman, M ;
Cunningham, ML ;
Fairlamb, AH ;
Hunter, WN .
STRUCTURE, 1999, 7 (01) :81-89
[9]   Phenothiazine inhibitors of trypanothione reductase as potential antitrypanosomal and antileishmanial drugs [J].
Chan, C ;
Yin, H ;
Garforth, J ;
McKie, JH ;
Jaouhari, R ;
Speers, P ;
Douglas, KT ;
Rock, PJ ;
Yardley, V ;
Croft, SL ;
Fairlamb, AH .
JOURNAL OF MEDICINAL CHEMISTRY, 1998, 41 (02) :148-156
[10]  
Chen SJ, 1997, BIOORG MED CHEM LETT, V7, P505