title: QSAR, QSPR and QSRR in Terms of 3-D-MoRSE Descriptors for In Silico Screening of Clofibric Acid Analogues.
abstract: A series of 27 analogues of clofibric acid, mostly heteroarylalkanoic derivatives, have been analyzed by a novel high-throughput reversed-phase HPLC method employing combined gradient of eluent's pH and organic modifier content. The such determined hydrophobicity (lipophilicity) parameters, log kw , and acidity constants, pKa , were subjected to multiple regression analysis to get a QSRR (Quantitative StructureRetention Relationships) and a QSPR (Quantitative Structure-Property Relationships) equation, respectively, describing these pharmacokinetics-determining physicochemical parameters in terms of the calculation chemistry derived structural descriptors. The previously determined in vitro log EC50 values - transactivation activity towards PPARα (human Peroxisome Proliferator-Activated Receptor α) - have also been described in a QSAR (Quantitative StructureActivity Relationships) equation in terms of the 3-D-MoRSE descriptors (3D-Molecule Representation of Structures based on Electron diffraction descriptors). The QSAR model derived can serve for an a priori prediction of bioactivity in vitro of any designed analogue, whereas the QSRR and the QSPR models can be used to evaluate lipophilicity and acidity, respectively, of the compounds, and hence to rational guide selection of structures of proper pharmacokinetics.
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Di Tullio
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Maccallini
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ammazzalorso
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Letizia
authors.initials: L
authors.lastname: Giampietro
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Amoroso
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: De Filippis
authors.affiliation: Department of Drug Sciences, University 'G. d'Annunzio', Chieti, Italy.
authors.forename: Marialuigia
authors.initials: M
authors.lastname: Fantacuzzi
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland phone/fax: +48 58 349 32 60.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Biopharmaceutics and Pharmacodynamics, Medical University of Gdańsk, Gdańsk, Poland phone/fax: +48 58 349 32 60. roman.kaliszan@gumed.edu.pl.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
keywords: Clofibric Acid Analogues; QSAR; QSPR; QSRR