A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies

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dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridSARI, SUAT/0000-0002-8248-4218
dc.authoridOzdemir, Zenyep/0000-0003-4559-2305
dc.authoridUTKU, Semra/0000-0003-3181-9134
dc.authorwosidSARI, SUAT/JCD-8070-2023
dc.authorwosidSARI, SUAT/A-5249-2017
dc.authorwosidOzdemir, Zenyep/AAJ-6384-2020
dc.authorwosidUTKU, Semra/F-7927-2015
dc.contributor.authorOzcelik, Azime Berna
dc.contributor.authorOzdemir, Zeynep
dc.contributor.authorSari, Suat
dc.contributor.authorUtku, Semra
dc.contributor.authorUysal, Mehtap
dc.date.accessioned2024-08-04T20:46:53Z
dc.date.available2024-08-04T20:46:53Z
dc.date.issued2019
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of cholinesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach. Method: We obtained our compounds by the reaction of various substituted/nonsubstituted benzenesulfonic acid derivatives with 6-substitutedphenyl-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman's method. Molecular docking studies were done using Glide and the results were evaluated on Maestro (Schrodinger, LLC, New York, NY, 2019). Results: The title compounds showed moderate inhibition at 100 mg/ml against both enzymes, yet with better activity against BChE. Compound VI2a emerged as a dual inhibitor with 25.02% and 51.70% inhibition against AChE and BChE, respectively. Conclusion: This study supports that novel pyridazinone derivates may be used for the development of new BChE inhibitory agents. It was less potent than the reference drugs, yet promising for further modifications as a lead. The ability of the compounds to adopt energetically more favourable conformations and to engage in more key interactions in the ECBChE active gorge explains their better activity profile against ECBChE. (C) 2019 Maj Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier B.V. All rights reserved.en_US
dc.identifier.doi10.1016/j.pharep.2019.07.006
dc.identifier.endpage1263en_US
dc.identifier.issn1734-1140
dc.identifier.issn2299-5684
dc.identifier.issue6en_US
dc.identifier.pmid31675671en_US
dc.identifier.scopus2-s2.0-85074141768en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1253en_US
dc.identifier.urihttps://doi.org/10.1016/j.pharep.2019.07.006
dc.identifier.urihttps://hdl.handle.net/11616/99003
dc.identifier.volume71en_US
dc.identifier.wosWOS:000502249300038en_US
dc.identifier.wosqualityQ2en_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.subjectAChE inhibitoren_US
dc.subjectBChE inhibitoren_US
dc.subject3(2H)-Pyridazinoneen_US
dc.subjectHydrazoneen_US
dc.subjectMolecular modellingen_US
dc.titleA new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studiesen_US
dc.typeArticleen_US

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