engleski

HPLC DETERMINATION OF THE STRUCTURAL FEATURES OF FLAVONOIDS RESPONSIBLE FOR THE BINDING TO THE HUMAN SERUM ALBUMIN

Flavonoids represent xenobiotics to which individuals are exposed through normal, everyday diet. Structurally, they are hydroxylated derivatives of benzopyran that have beneficial effects on human health. Due to the chemical variety of flavonoids as aglycones (deglycosylated forms of a flavonoid), as well as their possible glycosylation and methylation, studies of pharmacokinetic parameters represent a challenging area of research. In particular when referred to the understanding of the possible interactions of certain food constituents with drugs. In this study, we have determined the structural features of flavonoids relevant to the binding to human serum albumin (HSA) based on HPLC studies. A set of 20 flavonoids was analyzed by high-performance liquid chromatography with UV detection (HPLC-UV) to determine the retention parameters of each individual flavonoid. Chromatographic characterization was performed on a chiral-HSA column using a gradient method with the following timetable (t/min, B/%): (0.00), (3.30), (10.30), (10.50), (15.00) ; mobile phase A being 20 mmol/L K-phosphate pH 7.0 and mobile phase B 2-propanol. Elution was monitored at 280 nm. 155 molecular descriptors of flavonoids were generated using MOPAC 7, ACD/ChemSketch, ChemFileBrowser and TAM software. Statistical analysis was performed using Statistica v7.1, while prediction, based on random forests and leave-one-out external validation, has been made within R v2.8.1 environment. The percentage of flavonoid bound to HSA was calculated based on the retention time. For the set of the analyzed flavonoids the results varied from 71% to 85%. The most relevant molecular descriptors that describe interactions of flavonoids and HSA and possible pharmacophore were: bond order of C4-C5 bond, orbital electronegativity of the atom bound to C4 position, number of hydrogen bond donors, surface tension and density. The results indicate the importance of C4-C5 bond order as well as the orbital electronegativity of the atom bound to C4 – higher values indicate stronger affinity of the pharmacophore to bind to HSA. Hydrogen bond donors and physico-chemical descriptors imply importance of hydrogen bonds formation for the binding of a flavonoid to HSA.

HSA; flavonoids; SAR

nije evidentirano