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 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.
Girault
S
S
Institut de Biologie, URA CNRS 1309, Faculté de Pharmacie, Lille, France.
Davioud-Charvet
E
E
Salmon
L
L
Berecibar
A
A
Debreu
M A
MA
Sergheraert
C
C
D000818:Animals; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007202:Indicators and Reagents; D007700:Kinetics; D015394:Molecular Structure; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014349:Trypanosoma cruzi / Q000201:enzymology*
D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D014344:Trypanocidal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase