Hydrazide-Bridged Pyridazines for Cholinesterase Inhibitors: Synthesis, Characterizations, In Silico, and In Vitro Evaluation

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dc.authoridhepokur, ceylan/0000-0001-6397-1291
dc.authoridBozbey Merde, Irem/0000-0002-9290-938X
dc.authoridGURSOY, SULE/0000-0001-5236-5974
dc.authoridTaskor Onel, Gulce/0000-0002-9375-2329
dc.contributor.authorGursoy, Sule
dc.contributor.authorOnel, Gulce Taskor
dc.contributor.authorTurkmenoglu, Burcin
dc.contributor.authorMerde, Irem Bozbey
dc.contributor.authorDilek, Esra
dc.contributor.authorHepokur, Ceylan
dc.contributor.authorAlgul, Oztekin
dc.date.accessioned2024-10-26T18:07:54Z
dc.date.available2024-10-26T18:07:54Z
dc.date.issued2024
dc.departmentSivas Cumhuriyet Üniversitesi
dc.description.abstractIn this study, we investigate the inhibitory potential of a series of hydrazide derivatives bearing different substituents with the pyridazine structure (5 a-i and 6 a-f) against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) using a modified Ellman's method. The inhibitory profiles of the synthesized compounds were assessed by comparing their IC50 and Ki values. Our results demonstrate that all the compounds exhibit significant inhibitory activity against both AChE and BChE when compared to the reference compound, tacrine. Particularly, compound 6 a exhibited the highest activity against Electrophorus electricus AChE (EeAChE) with a Ki value of 3.26 nM, while compound 5 a displayed the most potent inhibition against equine BChE (eqBChE) with a Ki value of 0.94 nM. The compounds did not possess significant cytotoxicity action using the MTT assay on the cancer cell lines. The DPPH assays revealed that all the compounds have moderate antioxidant activities. Furthermore, molecular docking studies provided valuable insights into the interaction mechanisms of these compounds within the active sites of AChE and BChE crystal structures (PDB ID: 4EY7 and 4BDS, respectively). The above results indicated that the pyridazine-based compounds were a promising functional agent for the treatment of Alzheimer's disease. This study reveals the potential of hydrazide derivatives, each with distinct substituents on the pyridazine structure, as potent enzyme inhibitors (AChE and BChE) with antioxidant properties. The provided structural insights, inhibitory profiles, and molecular docking results emphasize their therapeutic potential for neurological disorders. These findings lay the groundwork for subsequent exploration and drug development within the domain of pyridazine compounds. image
dc.description.sponsorshipErzincan Binali Yimath;ldimath;rimath;m University [TSA-2021-758]
dc.description.sponsorshipThis study was funded by grants from Erzincan Binali Y & imath;ld & imath;r & imath;m University (grant number: TSA-2021-758). The authors would like to thank Erzincan Binali Y & imath;ld & imath;r & imath;m University, Basic Sciences Application and Research Center (EBYU-EUTAM) for the Schrodinger Maestro 2021-2 program. Also, the authors would like to thank Prof. Azime Berna Ozcelik for the HRMS analysis.
dc.identifier.doi10.1002/slct.202400085
dc.identifier.issn2365-6549
dc.identifier.issue12
dc.identifier.scopus2-s2.0-85188232941
dc.identifier.scopusqualityQ2
dc.identifier.urihttps://doi.org/10.1002/slct.202400085
dc.identifier.urihttps://hdl.handle.net/20.500.12418/29736
dc.identifier.volume9
dc.identifier.wosWOS:001191395900003
dc.identifier.wosqualityN/A
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.language.isoen
dc.publisherWiley-V C H Verlag Gmbh
dc.relation.ispartofChemistryselect
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectAcetylcholinesterase
dc.subjectbutyrylcholinesterase
dc.subjectpyridazine
dc.subjectN-benzylidenehydrazides
dc.subjectarylsulfonohydrazides
dc.subjectmolecular docking
dc.subjectAlzheimer's disease
dc.titleHydrazide-Bridged Pyridazines for Cholinesterase Inhibitors: Synthesis, Characterizations, In Silico, and In Vitro Evaluation
dc.typeArticle

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