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dc.creatorDobričić, Vladimir
dc.creatorMarković, Bojan
dc.creatorMilenković, Nikola
dc.creatorSavić, Vladimir
dc.creatorJaćević, Vesna
dc.creatorRancić, Nemanja
dc.creatorVladimirov, Sote
dc.creatorČudina, Olivera
dc.date.accessioned2019-09-02T11:39:49Z
dc.date.available2019-09-02T11:39:49Z
dc.date.issued2014
dc.identifier.issn0365-6233
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/2132
dc.description.abstractMolecular docking studies were performed on 18 17-carboxamide steroids in order to select compounds with potential local anti-inflammatory activity. These derivatives are amides of cortienic acids (obtained from hydrocortisone, prednisolone, and methylprednisolone) with methyl or ethyl esters of six amino acids. Interactions with the glucocorticoid receptor (GR), binding energies and ligand efficiency values of these compounds were compared with dexamethasone and cortienic acid obtained from prednisolone (inactive metabolite). On the basis of molecular docking studies, seven compounds were selected and their binding affinities for the GR were predicted by use of the exponential model created in this study. Subsequently, selected compounds were synthesized in good yields by use of modified N,N-dicyclohexylcarbodiimide (DCC)/1-hydroxybenzotriazole (HOBt) coupling procedure. Finally, the local anti-inflammatory activity of the synthesized compounds was examined by use of the croton oil-induced ear edema test. In vivo evaluation of systemic side effects as well as in silico prediction of metabolism were performed on the derivative with the best local anti-inflammatory activity. The combination of molecular docking studies and the exponential model for the GR binding affinity prediction could be used as an in silico tool for the rational design of novel 17-carboxamide steroids with potentially better biological profile than dexamethasone.en
dc.publisherWiley-VCH Verlag GMBH, Weinheim
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172041/RS//
dc.rightsrestrictedAccess
dc.sourceArchiv der Pharmazie
dc.subject17-Carboxamide steroidsen
dc.subjectGlucocorticoid receptor binding affinityen
dc.subjectLocal anti-inflammatory activityen
dc.subjectMolecular docking studiesen
dc.subjectSystemic side effectsen
dc.titleDesign, Synthesis, and Local Anti-Inflammatory Activity of 17 beta-Carboxamide Derivatives of Glucocorticoidsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЈаћевић, Весна; Добричић, Владимир; Савић, Владимир; Чудина, Оливера; Ранцић, Немања; Марковић, Бојан; Миленковић, Никола; Владимиров, Соте;
dc.citation.volume347
dc.citation.issue11
dc.citation.spage786
dc.citation.epage797
dc.citation.other347(11): 786-797
dc.citation.rankM22
dc.identifier.wos000344542200002
dc.identifier.doi10.1002/ardp.201400165
dc.identifier.pmid25159891
dc.identifier.scopus2-s2.0-84927137582
dc.identifier.rcubconv_3192
dc.type.versionpublishedVersion


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