title: Characterization of thymoquinone binding to human α₁-acid glycoprotein.
abstract: Thymoquinone (TQ) is the main bioactive component isolated from Nigella sativa essential oil and seeds and has been used for the treatment of inflammations, liver disorders, arthritis, and is of great importance as a promising therapeutic drug for different diseases including cancer. This paper reports the first experimental evidence on binding of TQ to human α(1)-acid glycoprotein (AGP), an important drug-binding glycoprotein in human plasma, which affects pharmacokinetic properties of various therapeutic agents. The interaction of TQ with AGP has been characterized by Fourier transform infrared (FTIR) and fluorescence spectroscopy, as well as by molecular docking experiments. FTIR spectroscopy showed that the binding of TQ to AGP slightly increases its thermal stability and shifts the existence of a molten globule-like state observed in a previous study to higher temperature. The binding constants K(a); the number of binding sites n; and the corresponding thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures were calculated through fluorescence spectroscopy. Fluorescence quenching experiments indicated that TQ binding involves hydrophobic interactions and to a lower extent hydrogen bonds, in agreement with molecular docking experiments. The data on binding ability of TQ to AGP represent basic information for the TQ pharmacokinetics such as drug metabolism and distribution in the body.
authors.affiliation: Scuola di Scienze del Farmaco e dei Prodotti della Salute, Università degli Studi di Camerino, Camerino, Italy.
authors.forename: Giulio
authors.initials: G
authors.lastname: Lupidi
authors.forename: Emidio
authors.initials: E
authors.lastname: Camaioni
authors.forename: Hamal
authors.initials: H
authors.lastname: Khalifé
authors.forename: Luca
authors.initials: L
authors.lastname: Avenali
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Damiani
authors.forename: Fabio
authors.initials: F
authors.lastname: Tanfani
authors.forename: Andrea
authors.initials: A
authors.lastname: Scirè
mesh_terms: D016227:Benzoquinones / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D031881:Nigella sativa / Q000737:chemistry*; D009961:Orosomucoid / Q000737:chemistry / Q000378:metabolism*; D010938:Plant Oils / Q000737:chemistry; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics; D029974:Carum
chemical_list: D016227:Benzoquinones; D009961:Orosomucoid; D010938:Plant Oils; C104525:caraway oil; C003466:thymoquinone