Synthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitors

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dc.authoridUSLU, HARUN/0000-0001-8827-8557
dc.authoridErikci, Acelya/0000-0001-9149-9510
dc.authoridKarakurt, Arzu/0000-0003-2209-0871
dc.authoridOzdemir, Zenyep/0000-0003-4559-2305
dc.authoridalagoz, mehmet abdullah/0000-0001-5190-7196;
dc.authorwosidUSLU, HARUN/P-3681-2019
dc.authorwosidErikci, Acelya/AAI-2965-2021
dc.authorwosidKarakurt, Arzu/ABH-9340-2020
dc.authorwosidOzdemir, Zenyep/AAJ-6384-2020
dc.authorwosidalagoz, mehmet abdullah/W-7847-2018
dc.authorwosidErikci, Acelya/I-8427-2013
dc.contributor.authorOzdemir, Zeynep
dc.contributor.authorAlagoz, Mehmet Abdullah
dc.contributor.authorUslu, Harun
dc.contributor.authorKarakurt, Arzu
dc.contributor.authorErikci, Acelya
dc.contributor.authorUcar, Gulberk
dc.contributor.authorUysal, Mehtap
dc.date.accessioned2024-08-04T20:47:12Z
dc.date.available2024-08-04T20:47:12Z
dc.date.issued2020
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground Since brain neurotransmitter levels are associated with the pathology of various neurodegenerative diseases like Parkinson and Alzheimer, monoamineoxidase (MAO) plays a critical role in balancing these neurotransmitters in the brain. MAO isoforms appear as promising drug targets for the development of central nervous system agents. Pyridazinones have a broad array of biological activities. Here, six pyridazinone derivatives were synthesized and their human monoamine oxidase inhibitory activities were evaluated by molecular docking studies, in silico ADME prediction and in vitro biological screening tests. Methods The compounds were synthesized by the reaction of different piperazine derivatives with 3 (2H)-pyridazinone ring and MAO-inhibitory effects were investigated. Docking studies were conducted with Maestro11.8 software. Results Most of the synthesized compounds inhibited hMAO-B selectively except compound 4f. Compounds 4a-4e inhibited hMAO-B selectively and reversibly in a competitive mode. Compound 4b was found as the most potent (k(i)=0.0220.001 mu M) and selective (SI (Ki (hMAO-A/hMAO-B))=206.82) hMAO-B inhibitor in this series. The results of docking studies were found to be consistent with the results of the in vivo activity studies. Compounds 4a-4e were found to be non-toxic to HepG2 cells at 25 mu M concentration. In silico calculations of ADME properties indicated that the compounds have good pharmacokinetic profiles. Conclusion It was concluded that 4b is possibly recommended as a promising nominee for the design and development of new pyridazinones which can be used in the treatment of neurological diseases.en_US
dc.description.sponsorshipInonu University Scientific Researches Unit [2011/80]en_US
dc.description.sponsorshipThis study was funded by Inonu University Scientific Researches Unit. (Project no: 2011/80).en_US
dc.identifier.doi10.1007/s43440-020-00070-w
dc.identifier.endpage704en_US
dc.identifier.issn1734-1140
dc.identifier.issn2299-5684
dc.identifier.issue3en_US
dc.identifier.pmid32144745en_US
dc.identifier.scopus2-s2.0-85080939339en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage692en_US
dc.identifier.urihttps://doi.org/10.1007/s43440-020-00070-w
dc.identifier.urihttps://hdl.handle.net/11616/99207
dc.identifier.volume72en_US
dc.identifier.wosWOS:000522884700001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherSpringer Heidelbergen_US
dc.relation.ispartofPharmacological Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectPyridazinoneen_US
dc.subjectMonoamine oxidase inhibitionen_US
dc.subjectMolecular dockingen_US
dc.titleSynthesis, molecular modelling and biological activity of some pyridazinone derivatives as selective human monoamine oxidase-B inhibitorsen_US
dc.typeArticleen_US

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