Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening.
A high-throughput screening campaign of a library of 100,000 lead-like compounds identified 2-iminobenzimidazoles as a novel class of trypanothione reductase inhibitors. These 2-iminobenzimidazoles display potent trypanocidal activity against Trypanosoma brucei rhodesiense, do not inhibit closely related human glutathione reductase and have low cytotoxicity against mammalian cells.
Holloway
Georgina A
GA
The Walter and Eliza Hall Institute of Medical Research, Biotechnology Centre, 4 Research Avenue, La Trobe Research and Development Park, Bundoora, Vic. 3086, Australia.
Baell
Jonathan B
JB
Fairlamb
Alan H
AH
Novello
Patrizia M
PM
Parisot
John P
JP
Richardson
John
J
Watson
Keith G
KG
Street
Ian P
IP
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001667:Binding, Competitive; D002470:Cell Survival / Q000187:drug effects; D020650:Combinatorial Chemistry Techniques; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D006801:Humans; D020128:Inhibitory Concentration 50; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects
D001562:Benzimidazoles; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase