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

doi:10.1016/j.bmcl.2006.11.090

Bioorganic & Medicinal Chemistry Letters

Volume 17, Issue 5, 1 March 2007, Pages 1422-1427

https://doi.org/10.1016/j.bmcl.2006.11.090 Get rights and content

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.

Graphical abstract

A high-throughput screening campaign of a library of 100,000 lead-like compounds identified 2-iminobenzimidazoles (L) 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.

Section snippets

Acknowledgments

This investigation received financial support from the UNICEF/UNDP/World Bank/WHO special program for research and training in tropical diseases (TDR). We gratefully acknowledge Bill Charman, the center for drug candidate optimization (CDCO), for advice, valuable discussion and encouragement. We also express our gratitude for the support of the TDR screening network, in particular Reto Brun and his group at the Swiss tropical institute for conducting the anti-trypanosomal and cytoxicity assays.

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

Abstract

Graphical abstract

Section snippets

Acknowledgments

Trends Parasitol.

J. Mol. Biol.

Adv. Drug Delivery Rev.

J. Biomol. Screen.

J. Biol. Chem.

Bioorg. Med. Chem. Lett.

Mini-Rev. Med. Chem.

Clin. Infect. Dis.

Clin. Microbiol. Rev.

Science

EMBO J.

Mol. Microbiol.

Curr. Top. Med. Chem.

Mol. Microbiol.

Eur. J. Biochem.

Biol. Chem.