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dc.creatorNikolić, Katarina
dc.creatorFilipić, Slavica
dc.creatorSmolinski, Adam
dc.creatorKaliszan, Roman
dc.creatorAgbaba, Danica
dc.date.accessioned2019-09-02T11:33:49Z
dc.date.available2019-09-02T11:33:49Z
dc.date.issued2013
dc.identifier.issn1482-1826
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/1901
dc.description.abstractPURPOSE. Rate of brain penetration (logPS), brain/plasma equilibration rate (logPS-brain), and extent of blood-brain barrier permeation (logBB) of 29 alpha-adrenergic and imidazoline-receptors ligands were examined in Quantitative-Structure-Property Relationship (QSPR) study. METHODS. Experimentally determined chromatographic retention data (logKw at pH 4.4, slope (S) at pH 4.4, logKw at pH 7.4, slope (S) at pH 7.4, logKw at pH 9.1, and slope (S) at pH 9.1) and capillary electrophoresis migration parameters (mu(eff) at pH 4.4, mu(eff) at pH 7.4, and mu(eff) at pH 9.1), together with calculated molecular descriptors, were used as independent variables in the QSPR study by use of partial least square (PLS) methodology. RESULTS. Predictive potential of the formed QSPR models, QSPR(logPS), QSPR(logPS-brain), QSPR(logBB), was confirmed by cross- and external validation. Hydrophilicity (Hy) and H-indices (H7m) were selected as significant parameters negatively correlated with both logPS and logPS-brain, while topological polar surface area (TPSA(NO)) was chosen as molecular descriptor negatively correlated with both logPS and logBB. The principal component analysis (PCA) and hierarchical clustering analysis (HCA) were applied to cluster examined drugs based on their chromatographic, electrophoretic and molecular properties. Significant positive correlations were obtained between the slope (S) at pH 7.4 and logBB in A/B cluster and between the logKw at pH 9.1 and logPS in C/D cluster. CONCLUSIONS. Results of the QSPR, clustering and correlation studies could be used as novel tool for evaluation of blood-brain barrier permeation of related alpha-adrenergic/imidazoline receptor ligands.en
dc.publisherCanadian Soc Pharmaceutical Sciences, Edmonton
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS//
dc.rightsopenAccess
dc.sourceJournal of Pharmacy and Pharmaceutical Sciences
dc.titlePartial Least Square and Hierarchical Clustering in ADMET Modeling: Prediction of Blood - Brain Barrier Permeation of alpha-Adrenergic and Imidazoline Receptor Ligandsen
dc.typearticle
dc.rights.licenseBY-SA
dcterms.abstractКалисзан, Роман; Николић, Катарина; Aгбаба, Даница; Филипић, Славица; Смолински, Aдам;
dc.citation.volume16
dc.citation.issue4
dc.citation.spage622
dc.citation.epage647
dc.citation.other16(4): 622-647
dc.citation.rankM23
dc.identifier.wos000327707500003
dc.identifier.doi10.18433/J3JK5P
dc.identifier.pmid24210068
dc.identifier.scopus2-s2.0-84887340023
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/675/1899.pdf
dc.identifier.rcubconv_2966
dc.type.versionpublishedVersion


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