Discovery of Novel Isoform-Selective Histone Deacetylases 5 and 9 Inhibitors Through Combined Ligand-Based Pharmacophore Modeling, Molecular Mocking, and Molecular Dynamics Simulations for Cancer Treatment

dc.contributor.author Elmezayen, Ammar D.
dc.contributor.author Yelekçi, Kemal
dc.contributor.author Al-Obaidi, Anas
dc.contributor.author Yelekçi, Kemal
dc.contributor.other Molecular Biology and Genetics
dc.date 2021-07
dc.date.accessioned 2021-06-12T20:07:36Z
dc.date.available 2021-06-12T20:07:36Z
dc.date.issued 2021-07
dc.date.issued 2021
dc.description.abstract Class IIa histone deacetylases (HDACs) 5 and 9 play crucial roles in several human disorders such as cancer, making them important targets for drug design. Continuous research is pursed to overcome the cytotoxicity side effect that comes with the currently available broad-spectrum HDACs inhibitors. Herein, common features of active HDACs inhibitors in clinical trials and use have been calculated to generate the best pharmacophore hypothesis. Guner-Henry scoring system was used to validate the generated hypotheses. Hypo1 of HDAC5 and Hypo2 of HDAC9 exhibited the most statistically significance hypotheses. Compounds with fit value of 3 and more were examined by QuickVina 2 docking tool to calculate their binding affinity toward all class IIa HDACs. A total of 6 potential selective compounds were subjected to 100 molecular dynamics (MD) simulation to examine their binding modes. The free binding energy calculations were computed according to the MM-PBSA method. Proposed selective compounds displayed good stability with their targets and thus they may offer potent leads for the designing of HDAC5 and HDAC9 isoform selective inhibitors. en_US
dc.identifier.citationcount 2
dc.identifier.doi 10.1016/j.jmgm.2021.107937 en_US
dc.identifier.issn 1093-3263
dc.identifier.issn 1093-3263 en_US
dc.identifier.pmid 34049193 en_US
dc.identifier.scopus 2-s2.0-85106925494 en_US
dc.identifier.scopusquality Q2
dc.identifier.uri https://hdl.handle.net/20.500.12469/4041
dc.identifier.volume 106 en_US
dc.identifier.wos WOS:000661885700003 en_US
dc.institutionauthor Elmezayen, Ammar D. en_US
dc.institutionauthor Al-Obaidi, Anas en_US
dc.institutionauthor Yelekçi, Kemal en_US
dc.language.iso en en_US
dc.publisher Elsevier en_US
dc.relation.journal Journal of Molecular Graphics and Modelling en_US
dc.relation.publicationcategory Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı en_US
dc.rights info:eu-repo/semantics/closedAccess en_US
dc.scopus.citedbyCount 4
dc.subject HDAC5 en_US
dc.subject HDAC9 en_US
dc.subject MD simulation en_US
dc.subject MM-PBSA en_US
dc.subject Pharmacophore modeling en_US
dc.title Discovery of Novel Isoform-Selective Histone Deacetylases 5 and 9 Inhibitors Through Combined Ligand-Based Pharmacophore Modeling, Molecular Mocking, and Molecular Dynamics Simulations for Cancer Treatment en_US
dc.type Article en_US
dc.wos.citedbyCount 3
dspace.entity.type Publication
relation.isAuthorOfPublication 9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery 9407938e-3d31-453b-9199-aaa8280a66c5
relation.isOrgUnitOfPublication 71ce8622-7449-4a6a-8fad-44d881416546
relation.isOrgUnitOfPublication.latestForDiscovery 71ce8622-7449-4a6a-8fad-44d881416546

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