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

Christopher J D Austin; Michael Moir; Jan Kahlert; Jason R. Smith; Joanne F. Jamie; Michael Kassiou; Louis M. Rendina

doi:10.1071/CH15489

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

Christopher J D Austin, Michael Moir, Jan Kahlert, Jason R. Smith, Joanne F. Jamie, Michael Kassiou, Louis M. Rendina^*

^*Corresponding author for this work

Faculty of Science and Engineering

Research output: Contribution to journal › Article › peer-review

5 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1866-1870
Number of pages	5
Journal	Australian Journal of Chemistry
Volume	68
Issue number	12
DOIs	https://doi.org/10.1071/CH15489
Publication status	Published - 2015

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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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AU - Austin, Christopher J D

AU - Moir, Michael

AU - Kahlert, Jan

AU - Smith, Jason R.

AU - Jamie, Joanne F.

AU - Kassiou, Michael

AU - Rendina, Louis M.

PY - 2015

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AB - 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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JO - Australian Journal of Chemistry

JF - Australian Journal of Chemistry

IS - 12

ER -

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

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