Advanced Search

Show simple item record

dc.contributor.authorElmezayen, Ammar D.
dc.contributor.authorKemal, Yelekçi
dc.date.accessioned2021-05-28T16:34:41Z
dc.date.available2021-05-28T16:34:41Z
dc.date.issued2021
dc.identifier.issn1476-9271en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/4032
dc.description.abstractThe fundamental cause of human cancer is strongly influenced by down- or up-regulations of epigenetic factors. Upregulated histone deacetylases (HDAC) have been shown to be effectively neutralized by the action of HDACs inhibitors (HDACi). However, cytotoxicity has been reported in normal cells because of non-specificity of several available HDACis that are in clinical use or at different phases of clinical trials. Because of the high amino acid sequence and structural similarity among HDAC enzymes, it is believed to be a challenging task to obtain isoform-selectivity. The essential aim of the present research work was to identify isoform-selective inhibitors against class IIa HDACs via structure-based drug design. Based on the highest binding affinity and isoform-selectivity, the top-ranked inhibitors were in silico tested for their absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties, which were classified as drug-like compounds. Later, molecular dynamics simulation (MD) was carried out for all compound-protein complexes to evaluate the structural stability and the biding mode of the inhibitors, which showed high stability throughout the 100 ns simulation. Free binding energy predictions by MM-PBSA method showed the high binding affinity of the identified compounds toward their respective targets. Hence, these inhibitors could be used as drug candidates or as lead compounds for more in silico or in vitro optimization to design safe isoform-selective HDACs inhibitors.en_US
dc.language.isoengen_US
dc.publisherElsevier Ltden_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectADMETen_US
dc.subjectMD simulationen_US
dc.subjectMM-PBSAen_US
dc.subjectSelective HDAC inhibitorsen_US
dc.subjectStructure-based virtual screeningen_US
dc.titleStructure-based virtual screening for novel potential selective inhibitors of class IIa histone deacetylases for cancer treatmenten_US
dc.typearticleen_US
dc.relation.journalComputational Biology and Chemistryen_US
dc.identifier.volume92en_US
dc.identifier.wosWOS:000656579000001en_US
dc.identifier.doi10.1016/j.compbiolchem.2021.107491en_US
dc.identifier.scopus2-s2.0-85105694556en_US
dc.institutionauthorElmezayen, Ammar D.en_US
dc.institutionauthorKemal, Yelekçien_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.identifier.pmid33930743en_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record