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dc.creatorŠegan, Sandra
dc.creatorTrifković, Jelena
dc.creatorVerbić, Tatjana
dc.creatorOpsenica, Dejan
dc.creatorZlatović, Mario
dc.creatorBurnett, James
dc.creatorŠolaja, Bogdan
dc.creatorMilojković-Opsenica, Dušanka
dc.date.accessioned2019-01-30T17:36:52Z
dc.date.available2019-01-30T17:36:52Z
dc.date.issued2013
dc.identifier.issn0731-7085
dc.identifier.urihttp://cer.ihtm.bg.ac.rs/handle/123456789/1305
dc.description.abstractThe physicochemical properties, retention parameters (R-M(0)), partition coefficients (log P-OW), and pK(a) values for a series of thirteen 1,7-bis(aminoalkyl) diazachrysene (1,7-DAAC) derivatives were determined in order to reveal the characteristics responsible for their biological behavior. The investigated compounds inhibit three unrelated pathogens (the Botulinum neurotoxin serotype A light chain (BoNT/A LC), Plasmodium falciparum malaria, and Ebola filovirus) via three different mechanisms of action. To determine the most influential factors governing the retention and activities of the investigated diazachrysenes, R-M(0), log P-OW, and biological activity values were correlated with 2D and 3D molecular descriptors, using a partial least squares regression. The resulting quantitative structure-retention (property) relationships indicate the importance of descriptors related to the hydrophobicity of the molecules (e.g., predicted partition coefficients and hydrophobic surface area). Quantitative structure-activity relationship models for describing biological activity against the BoNT/A LC and malarial strains also include overall compound polarity, electron density distribution, and proton donor/acceptor potential. Furthermore, models for Ebola filovirus inhibition are presented qualitatively to provide insights into parameters that may contribute to the compounds' antiviral activities. Overall, the models form the basis for selecting structural features that significantly affect the compound's absorption, distribution, metabolism, excretion, and toxicity profiles.en
dc.publisherElsevier Science Bv, Amsterdam
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172008/RS//
dc.relationNational Cancer Institute, National Institutes of Health (USA) [HHSN261200800001E]
dc.relationNATOs Public Diplomacy Division [SfP983638]
dc.rightsrestrictedAccess
dc.sourceJournal of Pharmaceutical and Biomedical Analysis
dc.subject1,7-Bis(aminoalkyl)-diazachrysene derivatives (1,7-DAAC)en
dc.subjectLipophilicityen
dc.subjectAcidity constantsen
dc.subjectQuantitative structure-retention relationship (QSRR)en
dc.subjectQuantitative structure-activity relationship (QSAR)en
dc.titleCorrelation between structure, retention, property, and activity of biologically relevant 1,7-bis(aminoalkyl)diazachrysene derivativesen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractЗлатовиц, Марио; Солаја, Богдан; Шеган, Сандра; Опсеница, Дејан; Милојковиц-Опсеница, Дусанка; Трифковиц, Јелена; Вербиц, Татјана; Бурнетт, Јамес;
dc.citation.volume72
dc.citation.spage231
dc.citation.epage239
dc.citation.other72: 231-239
dc.citation.rankM21
dc.identifier.pmid22985530
dc.identifier.doi10.1016/j.jpba.2012.08.025
dc.identifier.rcubConv_2881
dc.identifier.scopus2-s2.0-84869079937
dc.identifier.wos000311819100033
dc.type.versionpublishedVersion


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