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dc.creatorVučićević, Jelica
dc.creatorNikolić, Katarina
dc.creatorDobričić, Vladimir
dc.creatorAgbaba, Danica
dc.date.accessioned2019-09-02T11:46:26Z
dc.date.available2019-09-02T11:46:26Z
dc.date.issued2015
dc.identifier.issn0928-0987
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2380
dc.description.abstractImidazoline receptor ligands are a numerous family of biologically active compounds known to produce central hypotensive effect by interaction with both alpha(2)-adrenoreceptors (alpha(2)-AR) and imidazoline receptors (IRs). Recent hypotheses connect those ligands with several neurological disorders. Therefore some IRs ligands are examined as novel centrally acting antihypertensives and drug candidates for treatment of various neurological diseases. Effective Blood-Brain Barrier (BBB) permeability (P-e) of 18 IRs/alpha-ARs ligands and 22 Central Nervous System (CNS) drugs was experimentally determined using Parallel Artificial Membrane Permeability Assay (PAMPA) and studied by the Quantitative-Structure-Permeability Relationship (QSPR) methodology. The dominant molecules/cations species of compounds have been calculated at pH = 7.4. The analyzed ligands were optimized using Density Functional Theory (B3LYP/6-31G(d,p)) included in ChemBio3D Ultra 13.0 program and molecule descriptors for optimized compounds were calculated using ChemBio3D Ultra 13.0, Dragon 6.0 and ADMET predictor 6.5 software. Effective permeability of compounds was used as dependent variable (Y), while calculated molecular parametres were used as independent variables (X) in the QSPR study. SIMCA P+ 12.0 was used for Partial Least Square (PLS) analysis, while the stepwise Multiple Linear Regression (MLR) and Artificial Neural Networks (ANN) modeling were performed using STASTICA Neural Networks 4.0. Predictive potential of the formed models was confirmed by Leave-One-Out Cross- and external-validation and the most reliable models were selected. The descriptors that are important for model building are identified as well as their influence on BBB permeability. Results of the QSPR studies could be used as time and cost efficient screening tools for evaluation of BBB permeation of novel alpha-adrenergic/imidazoline receptor ligands, as promising drug candidates for treatment of hypertension or neurological diseases.en
dc.publisherElsevier Science BV, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS//
dc.rightsrestrictedAccess
dc.sourceEuropean Journal of Pharmaceutical Sciences
dc.subjectImidazoline ligandsen
dc.subjectPAMPAen
dc.subjectBlood-brain barrier permeabilityen
dc.subjectQSPRen
dc.titlePrediction of blood-brain barrier permeation of alpha-adrenergic and imidazoline receptor ligands using PAMPA technique and quantitative-structure permeability relationship analysisen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractДобричић, Владимир; Николић, Катарина; Aгбаба, Даница; Вучићевић, Јелица;
dc.citation.volume68
dc.citation.spage94
dc.citation.epage105
dc.citation.other68: 94-105
dc.citation.rankM21
dc.identifier.wos000349272000012
dc.identifier.doi10.1016/j.ejps.2014.12.014
dc.identifier.pmid25542610
dc.identifier.scopus2-s2.0-84920773866
dc.identifier.rcubconv_3262
dc.type.versionpublishedVersion


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