The first indoleamine-2,3-dioxygenase-1 (IDO1) inhibitors containing carborane

• Published in: Dalton transactions : an international journal of inorganic chemistry Vol. 43; no. 28; p. 10719
• Main Authors: Austin, Christopher J D, Kahlert, Jan, Issa, Fatiah, Reed, John H, Smith, Jason R, Ioppolo, Joseph A, Ong, Jennifer A, Jamie, Joanne F, Hibbs, David, Rendina, Louis M
• Format: Journal Article
• Language: English
• Published: England 28-07-2014
• Subjects: Boron Compounds - chemical synthesis; Boron Compounds - chemistry; Boron Compounds - pharmacology; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Indoleamine-Pyrrole 2,3,-Dioxygenase - antagonists & inhibitors; Molecular Docking Simulation; Naphthoquinones - chemical synthesis; Naphthoquinones - chemistry; Naphthoquinones - pharmacology; X-Ray Diffraction
• ISSN: 1477-9234
• DOI: 10.1039/c4dt00444b

Indoleamine-2,3-dioxygenase-1 (IDO1) is a critical immunoregulatory enzyme responsible for the metabolism of tryptophan during inflammation and disease. Based upon a pyranonaphthoquinone framework, the first examples of indoleamine-2,3-dioxygenase-1 (IDO1) inhibitors containing a carborane cage are reported. The novel closo-1,2-carboranyl-N-pyranonaphthoquinone derivatives display low μM binding affinity for the human recombinant enzyme, with IC50 values ranging from 0.78 to 1.77 μM.