Effects of conjugation metabolism on radical scavenging and transport properties of quercetin – In silico study

• Published in: Journal of molecular graphics & modelling 2019-01, Vol.86, p.278-285
• Main Authors: Stepanić, Višnja, Matić, Sara, Amić, Ana, Lučić, Bono, Milenković, Dejan, Marković, Zoran
• Format: Article
• Language: English
• Subjects: Conjugation metabolism; Disproportionation; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; Humans; Metabolic Detoxication, Phase II; Models, Chemical; Molecular Docking Simulation; Molecular Dynamics Simulation; Molecular Structure; Quantitative Structure-Activity Relationship; Quantum Theory; Quercetin; Quercetin - chemistry; Quercetin - pharmacology; Radical scavenging; Serum albumin; Serum Albumin, Human - chemistry
• ISSN: 1093-3263; 1873-4243
• DOI: 10.1016/j.jmgm.2018.10.023

Quercetin (Q) is a natural polyphenol with high radical scavenging capacity, but low in vivo bioavailability. It is extensively transformed by host phase II metabolism and microbiota. Herein, effects of major in vitro and in vivo conjugation transformations of Q on its radical scavenging capacity and human serum albumin (HSA) binding were studied by using appropriate computational approaches, DFT (U)B3LYP/6-31 + G(d,p) and molecular docking, respectively. With regard to radical scavenging capacity of Q, conjugation transformations generally reduce its antioxidant capacity including regeneration efficiency through disproportionation of an intermediate radical species since these structural modifications occur mainly at its radical scavenging –OH groups. They were also found to alter dominant radical scavenging mechanism in a specific way dependent upon conjugation type and site. Concerning distribution by HSA, binding to this main plasma transporter protein may not be dominant transport mechanism for Q and its metabolites in vivo. Like Q aglycon, most of its metabolites are bound non-specifically at multiple binding sites of HSA, with relatively weak affinities. Only sulfo-conjugates including plasma abundant isomer Q-3′-O-SO3–, were predicted to bind specifically in warfarin-like manner, but also with relatively low binding affinity. [Display omitted] •Radical scavenging (RS) properties of quercetin (Q) are altered by metabolism.•Dominant RS mechanism of metabolites depends on conjugation type and site.•Disproportionation regeneration of scavenging form is most efficient for aglycon.•Only sulfoconjugates bind specifically to human serum albumin (HSA).•RS properties of Q and its metabolites may be retained in the HSA bound state.