title: In vitro prediction of gastrointestinal absorption of novel β-hydroxy-β-arylalkanoic acids using PAMPA technique.
abstract: Prediction of gastrointestinal absorption of thirteen newly synthesized β-hydroxy-β-arylalkanoic acids (HAA) and ibuprofen was performed using PAMPA test. The highest values of PAMPA parameters (%T and Papp) were calculated for 1C, 1B and 2C and these parameters were significantly lower in comparison to ibuprofen. QSPR analysis was performed in order to identify molecular descriptors with the highest influence on %T and -logPappand to create models which could be used for the design of novel HAA with improved gastrointestinal absorption. Obtained results indicate that introduction of branched side chain, as well as introduction of substituents on one phenyl ring (which disturb symmetry of the molecule) could have positive impact on gastrointestinal absorption. On the basis of these results, six novel HAA were designed and PAMPA parameters %T and -logPappwere predicted by use of selected QSPR models. Designed derivatives should have better gastrointestinal absorption than HAA tested in this study.
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. 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: 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 Organic Chemistry, University of Belgrade, Faculty of Pharmacy, Vojvode Stepe 450, 11000 Belgrade, Serbia.
authors.forename: Sanda
authors.initials: S
authors.lastname: Dilber
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: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000378:metabolism; D065569:Gastrointestinal Absorption; D006880:Hydroxy Acids / Q000737:chemistry* / Q000378:metabolism; D007052:Ibuprofen / Q000737:chemistry* / Q000378:metabolism; D008567:Membranes, Artificial; D016571:Neural Networks, Computer; D010539:Permeability; D021281:Quantitative Structure-Activity Relationship
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D006880:Hydroxy Acids; D008567:Membranes, Artificial; D007052:Ibuprofen
keywords: Gastrointestinal absorption; PAMPA; Quantitative structure-permeability relationship; β-hydroxy-β-arylalkanoic acids