Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening

Georgina A Holloway; Jonathan B Baell; Alan H Fairlamb; Patrizia M Novello; John P Parisot; John Richardson; Keith G Watson; Ian P Street

doi:10.1016/j.bmcl.2006.11.090

Discovery of 2-iminobenzimidazoles as a new class of trypanothione reductase inhibitor by high-throughput screening

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1422-7. doi: 10.1016/j.bmcl.2006.11.090. Epub 2006 Dec 3.

Authors

Georgina A Holloway¹, Jonathan B Baell, Alan H Fairlamb, Patrizia M Novello, John P Parisot, John Richardson, Keith G Watson, Ian P Street

Affiliation

¹ The Walter and Eliza Hall Institute of Medical Research, Biotechnology Centre, 4 Research Avenue, La Trobe Research and Development Park, Bundoora, Vic. 3086, Australia.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Benzimidazoles / chemistry*
Benzimidazoles / pharmacology*
Benzimidazoles / toxicity
Binding, Competitive
Cell Survival / drug effects
Combinatorial Chemistry Techniques
Drug Evaluation, Preclinical / methods*
Humans
Inhibitory Concentration 50
NADH, NADPH Oxidoreductases / antagonists & inhibitors*
Structure-Activity Relationship
Trypanosoma brucei rhodesiense / drug effects

Substances

Benzimidazoles
NADH, NADPH Oxidoreductases
trypanothione reductase

Abstract

Publication types

MeSH terms

Substances

Grants and funding