title: Interaction of Carthamus tinctorius lignan arctigenin with the binding site of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase.
abstract: Mediterranean Carthamus tinctorius (Safflower) is used for treatment of inflammatory conditions and neuropsychiatric disorders. Recently C. tinctorius lignans arctigenin and trachelogenin but not matairesinol were described to interfere with the activity of tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) in peripheral blood mononuclear cells in vitro. We examined a potential direct influence of compounds on IDO enzyme activity applying computational calculations based on 3D geometry of the compounds. The interaction pattern analysis and force field-based minimization was performed within LigandScout 3.03, the docking simulation with MOE 2011.10 using the X-ray crystal structure of IDO. Results confirm the possibility of an intense interaction of arctigenin and trachelogenin with the binding site of the enzyme, while matairesinol had no such effect.
authors.affiliation: University of Innsbruck, Institute of Pharmacy/Pharmacognosy, CCB Innrain 80/82, Innsbruck 6020, Austria.
authors.forename: Veronika
authors.initials: V
authors.lastname: Temml
authors.forename: Susanne
authors.initials: S
authors.lastname: Kuehnl
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Stefan
authors.initials: S
authors.lastname: Schwaiger
authors.forename: Hermann
authors.initials: H
authors.lastname: Stuppner
authors.forename: Dietmar
authors.initials: D
authors.lastname: Fuchs
keywords: 1-MT, d-1-methyl tryptophan; 5-HT, 5-hydroxytryptamine, serotonin; Carthamus tinctorius; GBVI/WSA, generalized-born volume integral/weighted surface area; IDO, indoleamine 2,3-dioxygenase; IFN-γ, interferon-γ; Indoleamine-2,3-dioxygenase; Kyn/Trp, kynurenine to tryptophan ratio; Lignan; MMFF94, Merck Molecular Force Field 94; PBMC, peripheral blood mononuclear cells; TDO, tryptophan 2,3-dioxygenase; Treg, regulatory T-cells