New pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase: Synthesis biological evaluation and structural determinants of MAO-A and MAO-B selectivity

dc.contributor.authorYelekçi, Kemal
dc.contributor.authorKoyunoğlu, Semra
dc.contributor.authorYabanoğlu-Çiftçi, Samiye
dc.contributor.authorYelekçi, Kemal
dc.contributor.authorÖzgen, Özen
dc.contributor.authorUçar, Gülberk
dc.contributor.authorErol, Kevser
dc.contributor.authorKendi, Engin
dc.contributor.authorYeşilada, Akguel
dc.contributor.otherYelekçi, Kemal
dc.date.accessioned2019-06-27T08:05:41Z
dc.date.available2019-06-27T08:05:41Z
dc.date.issued2009
dc.departmentFakülteler, Mühendislik ve Doğa Bilimleri Fakültesi, Biyoinformatik ve Genetik Bölümüen_US
dc.description.abstractA new series of pyrazoline derivatives were prepared starting from a quinazolinone ring and evaluated for antidepressant anxiogenic and MAO-A and -B inhibitory activities by in vivo and in vitro tests respectively. Most of the synthesized compounds showed high activity against both the MAO-A (compounds 4a-4h 4j-4n and 5g-5l) and the MAO-B (compounds 4i and 5a-5f) isoforms. However none of the novel compounds showed antidepressant activity except for 4b. The reason for such biological properties was investigated by computational methods using recently published crystallographic models of MAO-A and MAO-B. The differences in the intermolecular hydrophobic and H-bonding of ligands to the active site of each MAO isoform were correlated to their biological data. Compounds 4i 4k 5e 5i and 5l were chosen for their ability to reversibly inhibit MAO-B and MAO-A and the availability of experimental inhibition data. Observation of the docked positions of these ligands revealed interactions with many residues previously reported to have an effect on the inhibition of the enzyme. Among the pyrazoline derivatives it appears that the binding interactions for this class of compounds are mostly hydrophobic. All have potential edge-to-face hydrophobic interactions with F343 as well as pi-pi stacking with Y398 and other hydrophobic interactions with L171. Strong hydrophobic and H-bonding interactions in the MAO recognition of 4i could be the reason why this compound shows selectivity toward the MAO-B isoform. The very high MAO-B selectivity for 4i can be also explained in terms of the distance between the FAD and the compound which was greater in the complex of MAO-A-4i as compared to the corresponding MAO-B complex. (C) 2008 Elsevier Ltd. All rights reserved.en_US]
dc.identifier.citation123
dc.identifier.doi10.1016/j.bmc.2008.11.068en_US
dc.identifier.endpage689
dc.identifier.issn0968-0896en_US
dc.identifier.issn1464-3391en_US
dc.identifier.issn0968-0896
dc.identifier.issn1464-3391
dc.identifier.issue2
dc.identifier.pmid19091581en_US
dc.identifier.scopus2-s2.0-58549107997en_US
dc.identifier.scopusqualityQ2
dc.identifier.startpage675en_US
dc.identifier.urihttps://hdl.handle.net/20.500.12469/1105
dc.identifier.urihttps://doi.org/10.1016/j.bmc.2008.11.068
dc.identifier.volume17en_US
dc.identifier.wosWOS:000262708300030en_US
dc.identifier.wosqualityQ2
dc.language.isoenen_US
dc.publisherPergamon-Elsevier Science Ltden_US
dc.relation.journalBioorganic & Medicinal Chemistryen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject2-Pyrazolineen_US
dc.subjectMAO-A/MAO-B inhibitionen_US
dc.subjectDockingen_US
dc.subjectAntidepressant-anxiogenic activitiesen_US
dc.subjectCrystallographic modelen_US
dc.titleNew pyrazoline bearing 4(3H)-quinazolinone inhibitors of monoamine oxidase: Synthesis biological evaluation and structural determinants of MAO-A and MAO-B selectivityen_US
dc.typeArticleen_US
dspace.entity.typePublication
relation.isAuthorOfPublication9407938e-3d31-453b-9199-aaa8280a66c5
relation.isAuthorOfPublication.latestForDiscovery9407938e-3d31-453b-9199-aaa8280a66c5

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