Polyamines with N-(3-phenylpropyl) substituents are effective competitive inhibitors of trypanothione reductase and trypanocidal agents

被引：50

作者：

Li, ZL

Fennie, MW

Ganem, B

Hancock, MT

Kobaslija, M

Rattendi, D

Bacchi, CJ

O'Sullivan, MC

机构：

[1] Canisius Coll, Dept Chem & Biochem, Buffalo, NY 14208 USA

[2] Indiana State Univ, Dept Chem, Terre Haute, IN 47809 USA

[3] Cornell Univ, Baker Lab, Dept Chem & Biol Chem, Ithaca, NY 14853 USA

[4] Pace Univ, Haskins Labs, New York, NY 10038 USA

[5] Pace Univ, Dept Biol, New York, NY 10038 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2001年 / 11卷 / 02期

关键词：

D O I：

10.1016/S0960-894X(00)00643-0

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Several N-(3-phenylpropyl)-substituted spermidine and spermine derivatives were prepared and found to be potent competitive inhibitors of Trypanosoma cruzi trypanothione reductase (seven compounds with K-i values < 5 <mu>M are described). The most effective inhibitor studied was compound 12 with a K-i value of 0.151 muM. Six of the compounds described are also effective trypanocides with IC50 values <1 <mu>M. (C) 2001 Elsevier Science Ltd. All rights reserved.

引用

收藏

页码：251 / 254

页数：4

相关论文

共 37 条

[1] Reductive amination of aldehydes and ketones with sodium triacetoxyborohydride. Studies on direct and indirect reductive amination procedures [J].

AbdelMagid, AF ;

Carson, KG ;

Harris, BD ;

Maryanoff, CA ;

Shah, RD .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (11) :3849-3862

[2] 2-amino diphenylsulfides as inhibitors of trypanothione reductase: Modification of the side chain [J].

Baillet, S ;

Buisine, E ;

Horvath, D ;

Maes, L ;

Bonnet, B ;

Sergheraert, C .

BIOORGANIC & MEDICINAL CHEMISTRY, 1996, 4 (06) :891-899

[3] 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

[4] 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

[5] New spermine and spermidine derivatives as potent inhibitors of Trypanosoma cruzi trypanothione reductase [J].

Bonnet, B ;

Soullez, D ;

DavioudCharvet, E ;

Landry, V ;

Horvath, D ;

Sergheraert, C .

BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (07) :1249-1256

[6] 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

[7] Pharmacological approaches to antitrypanosomal chemotherapy [J].

Croft, SL .

MEMORIAS DO INSTITUTO OSWALDO CRUZ, 1999, 94 (02) :215-220

[8] Synthesis of polyamine derivatives for the preparation of affinity chromatography columns for the search of new Trypanosoma cruzi targets [J].

Davioud-Charvet, E ;

Berecibar, A ;

Girault, S ;

Landry, V ;

Drobecq, H ;

Sergheraert, C .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 1999, 9 (11) :1567-1572

[9] Charge is the major discriminating factor for glutathione reductase versus trypanothione reductase inhibitors [J].

Faerman, CH ;

Savvides, SN ;

Strickland, C ;

Breidenbach, MA ;

Ponasik, JA ;

Ganem, B ;

Ripoll, D ;

KrauthSiegel, RL ;

Karplus, PA .

BIOORGANIC & MEDICINAL CHEMISTRY, 1996, 4 (08) :1247-1253

[10]

FAIRLAMB AH, 1992, ANNU REV MICROBIOL, V46, P695, DOI 10.1146/annurev.micro.46.1.695

← 1 2 3 4 →