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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Quantitative structure-retention relationships of flavonoids unraveled by immobilized artificial membrane chromatography

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Santoro, Adriana Leandra [1] ; Carrilho, Emanuel [1, 2] ; Lancas, Fernando Mauro [1] ; Montanari, Carlos Alberto [1]
Total Authors: 4
[1] Univ Sao Paulo, Inst Quim Sao Carlos, BR-13566590 Sao Carlos, SP - Brazil
[2] Inst Nacl Ciencia & Tecnol Bioanalit, BR-13083970 Campinas, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: European Journal of Pharmaceutical Sciences; v. 88, p. 147-157, JUN 10 2016.
Web of Science Citations: 4

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 P-oct). 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 (k(IAM)) 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). (C) 2015 Elsevier B.V. All rights reserved. (AU)

FAPESP's process: 11/01893-3 - Optimizing trypanosomatid agents by integration of in silico, calorimetry and cell-based assays
Grantee:Carlos Alberto Montanari
Support type: Regular Research Grants