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dc.creatorRužić, Dušan
dc.creatorPetković, Miloš
dc.creatorAgbaba, Danica
dc.creatorGanesan, A.
dc.creatorNikolić, Katarina
dc.date.accessioned2019-09-02T12:11:55Z
dc.date.available2019-09-02T12:11:55Z
dc.date.issued2019
dc.identifier.issn1868-1743
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3369
dc.description.abstractHistone deacetylase 6 (HDAC6) is unique hydrolase within HDAC family, having pleiotropic deacetylase activity against alpha-tubulin, cortactin and dynein. Comprehensively, HDAC6 controls cell motility, apoptosis and protein folding, whereas alterations in its structure and function are related to the pathogenesis of cancer, neurodegeneration and inflammation. To define structural motifs which guide HDAC6 selectivity, we developed and compared three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models for HDAC1 and HDAC6 inhibitors. The reduction of the bias in conformer generation was supported by virtual docking study by using crystal structures of human HDAC1 and HDAC6 isoforms. Following these findings, the combined ligand-based and fragment-based drug design methodologies were used in the design of selective HDAC6 inhibitors. Group of the most promising novel ligands was selected based on the predicted HDAC6 selectivity, pharmacokinetic profile, synthetic tractability, and in silico cytotoxicity against the wide range of human cancer cell lines.en
dc.publisherWiley-VCH Verlag GMBH, Weinheim
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172033/RS//
dc.rightsrestrictedAccess
dc.sourceMolecular Informatics
dc.subjectRational drug designen
dc.subject3D-QSARen
dc.subjectEpidrugsen
dc.subjectHDAC6en
dc.titleCombined Ligand and Fragment-based Drug Design of Selective Histone Deacetylase-6 Inhibitorsen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractAгбаба, Даница; Ганесан, A.; Петковић, Милош; Ружић, Душан; Николић, Катарина;
dc.citation.volume38
dc.citation.issue5
dc.citation.other38(5): -
dc.citation.rankM21
dc.identifier.wos000466504900001
dc.identifier.doi10.1002/minf.201800083
dc.identifier.pmid30632697
dc.identifier.scopus2-s2.0-85059916833
dc.identifier.rcubconv_4362
dc.type.versionpublishedVersion


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