title: Application of biopartitioning micellar chromatography and QSRR modeling for prediction of gastrointestinal absorption and design of novel β-hydroxy-β-arylalkanoic acids.
abstract: Gastrointestinal absorption of thirteen novel β-hydroxy-β-arylalkanoic acids (HAA) with anti-inflammatory activity was predicted by use of biopartitioning micellar chromatography and compared to ibuprofen. All tested HAA have lower retention factors (k) and lower expected gastrointestinal absorption than ibuprofen, whereas derivatives with the highest values of k are 1C, 2APTF and 2C. Quantitative structure-retention relationship (QSRR) analysis was performed in order to identify molecular descriptors with the highest influence on k and ANN(k) model was selected as optimal. Descriptors which form this model (nBM, P_VSA_LogP_8 and Eta_L) indicate that replacement of phenyl ring with a saturated or partially unsaturated one, as well as presence of halogens and nitro group should positively affect k values. On the basis of these conclusions, six novel HAA were designed and selected QSRR model was used for the prediction of their k values.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia. Electronic address: vladimir@pharmacy.bg.ac.rs.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Dobričić
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Jelena
authors.initials: J
authors.lastname: Savić
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Nikolic
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Sote
authors.initials: S
authors.lastname: Vladimirov
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Zorica
authors.initials: Z
authors.lastname: Vujić
authors.affiliation: Department of Pharmaceutical Chemistry, University of Belgrade-Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Jasmina
authors.initials: J
authors.lastname: Brborić
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000493:pharmacokinetics*; D002845:Chromatography / Q000379:methods; D015195:Drug Design; D065569:Gastrointestinal Absorption; D006880:Hydroxy Acids / Q000737:chemistry / Q000493:pharmacokinetics*; D008823:Micelles; D008958:Models, Molecular; D016571:Neural Networks, Computer; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000893:Anti-Inflammatory Agents; D006880:Hydroxy Acids; D008823:Micelles
keywords: Biopartitioning micellar chromatography; Gastrointestinal absorption; Quantitative structure-retention relationship analysis; β-hydroxy-β-arylalkanoic acids