Parallel synthesis of a library of 1,4-naphthoquinones and automated screening of potential inhibitors of trypanothione reductase from Trypanosoma cruzi

被引：43

作者：

Salmon-Chemin, L ^{[1
]}

Lemaire, A ^{[1
]}

De Freitas, S ^{[1
]}

Deprez, B ^{[1
]}

Sergheraert, C ^{[1
]}

Davioud-Charvet, E ^{[1
]}

机构：

[1] Univ Lille 2, UMR 8525 CNRS, Inst Biol, Inst Pasteur, F-59021 Lille, France

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2000年 / 10卷 / 07期

关键词：

D O I：

10.1016/S0960-894X(00)00056-1

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Solid- and solution-phase parallel syntheses of 1,4-naphthoquinones (1,4-NQ) are described. A library of 1360 amides was constructed from the combination of 12 newly synthesised 1,4-NQ carboxylic acid and 120 amines, and was screened for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi. The most active hits from a primary screening were re-synthesised and confirmed. This approach proves that it is possible to design potent and highly specific TcTR inhibitors deriving From menadione, juglone and plumbagin. (C) 2000 Elsevier Science Ltd. All rights reserved.

引用

页码：631 / 635

页数：5

共 15 条

[1] SILVER(I)-CATALYZED OXIDATIVE DECARBOXYLATION OF ACIDS BY PEROXYDISULFATE - ROLE OF SILVER(II) [J].

ANDERSON, JM ;

KOCHI, JK .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1970, 92 (06) :1651-&

[2] MECHANISM OF REDUCTION OF QUINONES BY TRYPANOSOMA-CONGOLENSE TRYPANOTHIONE REDUCTASE [J].

CENAS, NK ;

ARSCOTT, D ;

WILLIAMS, CH ;

BLANCHARD, JS .

BIOCHEMISTRY, 1994, 33 (09) :2509-2515

[3] Synthesis of 5,5′-dithiobis(2-nitrobenzamides) as alternative substrates for trypanothione reductase and thioredoxin reductase:: A microtiter colorimetric assay for inhibitor screening [J].

Davioud-Charvet, E ;

Becker, K ;

Landry, V ;

Gromer, S ;

Logé, C ;

Sergheraert, C .

ANALYTICAL BIOCHEMISTRY, 1999, 268 (01) :1-8

[4]

DAVIOUDCHARVET E, 1998, Patent No. 9806541

[5] Disruption of the trypanothione reductase gene of Leishmania decreases its ability to survive oxidative stress in macrophages [J].

Dumas, C ;

Ouellette, M ;

Tovar, J ;

Cunningham, ML ;

Fairlamb, AH ;

Tamar, S ;

Olivier, M ;

Papadopoulou, B .

EMBO JOURNAL, 1997, 16 (10) :2590-2598

[6] SUBVERSIVE SUBSTRATES FOR THE ENZYME TRYPANOTHIONE DISULFIDE REDUCTASE - ALTERNATIVE APPROACH TO CHEMOTHERAPY OF CHAGAS-DISEASE [J].

HENDERSON, GB ;

ULRICH, P ;

FAIRLAMB, AH ;

ROSENBERG, I ;

PEREIRA, M ;

SELA, M ;

CERAMI, A .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (15) :5374-5378

[7]

Jacoby EM, 1996, PROTEINS, V24, P73, DOI 10.1002/(SICI)1097-0134(199601)24:1&lt

[8]

73::AID-PROT5&gt

[9]

3.0.CO

[10]

2-P

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