Structure-activity relationships in 2-aminodiphenylsulfides against trypanothione reductase from Trypanosoma cruzi

In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry letters 1998-05, Vol.8 (10), p.1175-1180
Main Authors: Girault, Sophie, Davioud-Charvet, Elisabeth, Salmon, Laurence, Berecibar, Amaya, Debreu, Marie-Ange, Sergheraert, Christian
Format: Article
Language:English
Subjects:
Animals
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiparasitic agents
Biological and medical sciences
Drug Design
Enzyme Inhibitors - chemical synthesis
Enzyme Inhibitors - chemistry
Enzyme Inhibitors - pharmacology
Indicators and Reagents
Kinetics
Medical sciences
Molecular Structure
NADH, NADPH Oxidoreductases - antagonists & inhibitors
Pharmacology. Drug treatments
Structure-Activity Relationship
Trypanocidal Agents - chemical synthesis
Trypanocidal Agents - chemistry
Trypanocidal Agents - pharmacology
Trypanosoma cruzi - enzymology
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Summary:In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed the importance of the aromatic rings and of the amino groups in the side chains for potent inhibition. Quinonic moities were also introduced with the aim of acting as TR redox-cycling substrates. In order to establish structural elements responsible for inhibition of trypanothione reductase (TR) from Trypanosoma cruzi by 2-aminodiphenylsulfides, a series of dissymmetrical derivatives, corresponding to the replacement of one aromatic moiety by different amines, was synthesized. TR inhibition studies revealed the importance of the aromatic rings and of the amino groups in the side chains for potent inhibition. Quinonic moities were also introduced with the aim of acting as TR redox-cycling substrates.
ISSN:0960-894X
1464-3405
DOI:10.1016/S0960-894X(98)00180-2