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

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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.

LanguageEnglish
Pages1866-1870
Number of pages5
JournalAustralian Journal of Chemistry
Volume68
Issue number12
DOIs
Publication statusPublished - 2015

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Indoleamine-Pyrrole 2,3,-Dioxygenase
Scaffolds
Lead compounds
Enzymes
Experiments

Cite this

Austin, Christopher J D ; Moir, Michael ; Kahlert, Jan ; Smith, Jason R. ; Jamie, Joanne F. ; Kassiou, Michael ; Rendina, Louis M. / Carborane-Containing Hydroxyamidine Scaffolds as Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 (IDO1). In: Australian Journal of Chemistry. 2015 ; Vol. 68, No. 12. pp. 1866-1870.
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Carborane-Containing Hydroxyamidine Scaffolds as Novel Inhibitors of Indoleamine 2,3-Dioxygenase 1 (IDO1). / Austin, Christopher J D; Moir, Michael; Kahlert, Jan; Smith, Jason R.; Jamie, Joanne F.; Kassiou, Michael; Rendina, Louis M.

In: Australian Journal of Chemistry, Vol. 68, No. 12, 2015, p. 1866-1870.

Research output: Contribution to journalArticleResearchpeer-review

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