title: Quantitative structure-retention relationships of flavonoids unraveled by immobilized artificial membrane chromatography.
abstract: The pharmacokinetic properties of flavonoids with differing degrees of lipophilicity were investigated using immobilized artificial membranes (IAMs) as the stationary phase in high performance liquid chromatography (HPLC). For each flavonoid compound, we investigated whether the type of column used affected the correlation between the retention factors and the calculated octanol/water partition (log Poct). Three-dimensional (3D) molecular descriptors were calculated from the molecular structure of each compound using i) VolSurf software, ii) the GRID method (computational procedure for determining energetically favorable binding sites in molecules of known structure using a probe for calculating the 3D molecular interaction fields, between the probe and the molecule), and iii) the relationship between partition and molecular structure, analyzed in terms of physicochemical descriptors. The VolSurf built-in Caco-2 model was used to estimate compound permeability. The extent to which the datasets obtained from different columns differ both from each other and from both the calculated log Poct and the predicted permeability in Caco-2 cells was examined by principal component analysis (PCA). The immobilized membrane partition coefficients (kIAM) were analyzed using molecular descriptors in partial least square regression (PLS) and a quantitative structure-retention relationship was generated for the chromatographic retention in the cholesterol column. The cholesterol column provided the best correlation with the permeability predicted by the Caco-2 cell model and a good fit model with great prediction power was obtained for its retention data (R(2)=0.96 and Q(2)=0.85 with four latent variables).
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil.
authors.forename: Adriana Leandra
authors.initials: AL
authors.lastname: Santoro
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil; Instituto Nacional de Ciência e Tecnologia de Bioanalítica, 13083-970, Campinas, SP, Brazil.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Carrilho
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil.
authors.forename: Fernando Mauro
authors.initials: FM
authors.lastname: Lanças
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil. Electronic address: Carlos.Montanari@usp.br.
authors.forename: Carlos Alberto
authors.initials: CA
authors.lastname: Montanari
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D018938:Caco-2 Cells; D002845:Chromatography / Q000379:methods*; D005419:Flavonoids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008567:Membranes, Artificial; D015394:Molecular Structure; D010539:Permeability; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D005419:Flavonoids; D008567:Membranes, Artificial
keywords: Flavonoids; Human colon epithelial cancer cell line; Immobilized artificial membrane chromatography; Partial least squares; Partition coefficient logarithm; Quantitative structure–property relationships