Show simple item record

dc.creatorNikolić, Katarina
dc.creatorFilipić, Slavica
dc.creatorAgbaba, Danica
dc.date.accessioned2019-09-02T11:14:51Z
dc.date.available2019-09-02T11:14:51Z
dc.date.issued2008
dc.identifier.issn0968-0896
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/1124
dc.description.abstractThe hypotensive effect of imidazoline ligands was attributed to both alpha(2)-adrenergic receptors and nonadrenergic imidazoline-1 receptors (I-1-R). Selective I-1-R ligands, devoid of the typical side effects of other centrally acting antihypertensive drugs, could be widely used in antihypertensive therapy. Thus, there is significant interest in developing new imidazoline analogs with higher selectivity and affinity for I-1-receptors. The quantitative structure-activity relationship (QSAR) study of 12 ligands was carried out using multilinear regression method on I-1-R and alpha(2)-adrenergic receptors binding affinities on human platelets. The compounds have been studied using Becke3LYP/3-21G (d, p) and Becke3LYP/6-31G(d, p) DFT methods. Among 42 descriptors that were considered in generating the QSAR model, three descriptors such as partial atomic charges of nitrogen in the heterocyclic moiety, distribution coefficient, and molar refractivity of the ligands resulted in a statistically significant model with R-2 = 0.935 and cross-validation parameter q(pre)(2) = 0.803. The validation of the QSAR models was done by cross-validation and external test set prediction. The developed multiple linear regression models for the I-1-R ligands were aimed to link the structures to their reported I-1-R binding affinity log(1/K-i). The theoretical approach indicates that an increase in distribution coefficient and molar refractivity value, together with a decrease in average N-charge in the heterocyclic moiety of the ligands, causes better binding affinity for active site of the I-1 receptors. The developed QSAR model is intended to predict I-1-R binding affinity of related compounds and to de. ne possible physicochemical, electronical, and structural requirements for selective I-1-receptor ligands.en
dc.publisherPergamon-Elsevier Science Ltd, Oxford
dc.relationinfo:eu-repo/grantAgreement/MESTD/MPN2006-2010/142071/RS//
dc.rightsrestrictedAccess
dc.sourceBioorganic & Medicinal Chemistry
dc.subjectI-1-receptoren
dc.subjectI-1-R ligandsen
dc.subjectcentrally acting antihypertensivesen
dc.subjectstructure activity relationshipen
dc.subjectpharmacophoreen
dc.titleQSAR study of imidazoline antihypertensive drugsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractФилипић, Славица; Aгбаба, Даница; Николић, Катарина;
dc.citation.volume16
dc.citation.issue15
dc.citation.spage7134
dc.citation.epage7140
dc.citation.other16(15): 7134-7140
dc.citation.rankM21
dc.identifier.wos000258749500006
dc.identifier.doi10.1016/j.bmc.2008.06.051
dc.identifier.pmid18621536
dc.identifier.scopus2-s2.0-84962448550
dc.identifier.rcubconv_2044
dc.type.versionpublishedVersion


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record