Integrated Binary QSAR-Driven Virtual Screening and In Vitro Studies for Finding Novel hMAO-B-Selective Inhibitors

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dc.authoridAksoydan, Busecan/0000-0002-7223-9366
dc.authoridDurdagi, Serdar/0000-0002-0426-0905
dc.authoridYurtsever, Mine/0000-0001-6504-7182
dc.authorwosidDurdagi, Serdar/B-6862-2009
dc.authorwosidSenturk, Murat/C-4491-2012
dc.authorwosidDurdagi, Serdar/J-1904-2018
dc.authorwosidYurtsever, Mine/O-3748-2014
dc.contributor.authorIs, Yusuf Serhat
dc.contributor.authorAksoydan, Busecan
dc.contributor.authorSenturk, Murat
dc.contributor.authorYurtsever, Mine
dc.contributor.authorDurdagi, Serdar
dc.date.accessioned2024-06-13T20:18:06Z
dc.date.available2024-06-13T20:18:06Z
dc.date.issued2020
dc.departmentİstanbul Gedik Üniversitesi
dc.description.abstractThe increased activity of monoamine oxidase (MAO) enzymes may lead to serious consequences since they reduce the level of neurotransmitters and are associated with severe neurodegenerative diseases. The inhibition of this enzyme, especially the B isoform, plays a vital role in the treatment of Parkinson's disease (PD). This study is aimed to find novel human MAO-B (hMAO-B) selective inhibitors. A total of 256.750 compounds from the Otava small molecules database were virtually screened gradually by employing several screening techniques for this purpose. Initially, a high-throughput virtual screening (HTVS) method was employed, and 10% of the molecules having high docking scores were subjected to binary QSAR models for further screening of their therapeutic activities against PD, Alzheimer's disease (AD), and depression as well as for their toxicity and pharmacokinetic properties. Then, enzyme selectivity of the ligands towards the A and B forms that passed through all the filters were studied using the induced-fit docking method and molecular dynamics simulations. At the end of this exhaustive research, we identified two hit molecules ligand3 (Otava ID: 7131545) and ligand4 (Otava ID: 7566820). Based on the in vitro results, these two compounds (ligands3 and 4) together with ligands 1 and 2 found in our previous study showed activity at the nanomolar (nM) level, and the results indicated that these four ligands inhibit hMAO-B better than the FDA-approved drug selegiline.
dc.identifier.doi10.1021/acs.jcim.0c00169
dc.identifier.endpage4055
dc.identifier.issn1549-9596
dc.identifier.issn1549-960X
dc.identifier.issue8
dc.identifier.pmid32672456
dc.identifier.scopus2-s2.0-85089806027
dc.identifier.scopusqualityQ1
dc.identifier.startpage4047
dc.identifier.urihttps://doi.org/10.1021/acs.jcim.0c00169
dc.identifier.urihttps://hdl.handle.net/11501/1228
dc.identifier.volume60
dc.identifier.wosWOS:000563791600031
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherAmer Chemical Soc
dc.relation.ispartofJournal of Chemical Information and Modeling
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectMonoamine-Oxidase-B
dc.subjectCovalently-Bound Flavin
dc.subjectParkinsons-Disease
dc.subjectCrystal-Structures
dc.subjectMao-A
dc.subjectProtein
dc.subjectPotent
dc.subjectDerivatives
dc.subjectPrediction
dc.subjectSubstrate
dc.titleIntegrated Binary QSAR-Driven Virtual Screening and In Vitro Studies for Finding Novel hMAO-B-Selective Inhibitors
dc.typeArticle

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