title: Benzofuranquinones as inhibitors of indoleamine 2,3-dioxygenase (IDO). Synthesis and biological evaluation.
abstract: A series of benzofuranquinones, analogues of the marine metabolite annulin A, has been synthesized and evaluated as inhibitors of human indoleamine 2,3-dioxygenase (IDO). The synthesis was carried out by copper(II)-mediated reaction of bromobenzoquinones with 1,3-dicarbonyl compounds followed by functional group interconversions. The most potent compounds were 5-methoxy-2-methylbenzofuranquinones containing a CH2OR group at position-3 with IC50 ~ 0.2 mM. The corresponding hydroquinones were inactive. Compounds based on the benzimidazolequinone framework are also active IDO inhibitors. The quinones do not generate significant levels of oxidative stress at concentrations that inhibit IDO.
authors.affiliation: School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK. c.j.moody@nottingham.ac.uk.
authors.forename: Catarina
authors.initials: C
authors.lastname: Carvalho
authors.forename: David
authors.initials: D
authors.lastname: Siegel
authors.forename: Martyn
authors.initials: M
authors.lastname: Inman
authors.forename: Rui
authors.initials: R
authors.lastname: Xiong
authors.forename: David
authors.initials: D
authors.lastname: Ross
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Moody
mesh_terms: D001572:Benzofurans / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011485:Protein Binding; D011809:Quinones / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014364:Tryptophan / Q000378:metabolism
chemical_list: D001572:Benzofurans; D004791:Enzyme Inhibitors; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D011809:Quinones; D014364:Tryptophan