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Australian Journal of Chemistry Australian Journal of Chemistry Society
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Carborane-Containing Hydroxyamidine Scaffolds as Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 (IDO1)

Christopher J. D. Austin A C , Michael Moir A C , Jan Kahlert A , Jason R. Smith B , Joanne F. Jamie B , Michael Kassiou A and Louis M. Rendina A D
+ Author Affiliations
- Author Affiliations

A School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia.

B Department of Chemistry and Biomolecular Sciences, Macquarie University, Sydney, NSW 2109, Australia.

C These authors contributed equally to the work in this paper.

D Corresponding author. Email: lou.rendina@sydney.edu.au

Australian Journal of Chemistry 68(12) 1866-1870 https://doi.org/10.1071/CH15489
Submitted: 11 August 2015  Accepted: 7 October 2015   Published: 9 November 2015

Abstract

Two new carborane-containing hydroxyamidines were prepared as potential inhibitors of the indoleamine 2,3-dioxygenase 1 (IDO1) enzyme. One compound (3) displayed low micromolar (1.90 μM) inhibition of IDO1, with the related compound (4) displaying >5-fold lower inhibitory activity, i.e. subtle differences in structure between the two carborane compounds led to dramatic changes in inhibitor binding. In silico docking experiments unravel a possible molecular mechanism that is consistent with the observed difference in IDO1 binding for 3 and 4 and also for the phenyl bioisosteres 1 and 2.


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