Rhodanine-pyridinium derivatives as a new category of cholinesterase inhibitors: Design, synthesis, in vitro and in silico enzymatic evaluations

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dc.contributor.authorNoori, Milad
dc.contributor.authorKarimian, Somaye
dc.contributor.authorDastyafteh, Navid
dc.contributor.authorGhafouri, Seyedeh Niloufar
dc.contributor.authorMohammadi-Khanaposhtani, Maryam
dc.contributor.authorSafapoor, Sajedeh
dc.contributor.authorGhomi, Minoo Khalili
dc.date.accessioned2026-04-04T13:35:03Z
dc.date.available2026-04-04T13:35:03Z
dc.date.issued2025
dc.departmentİnönü Üniversitesi
dc.description.abstractRhodanine-pyridinium derivatives 10a-q were designed and synthesized based on reported cholinesterase (ChE) inhibitors and evaluated as potent anti-Alzheimer's disease agents. The in vitro anti-ChE activity of the title compounds was evaluated against two main forms of this enzyme: acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The obtained in vitro results showed that all the synthesized derivatives were more potent than positive control tacrine against AChE. Moreover, most of the new synthesized compounds were more potent than tacrine against BChE. Among the synthesized compounds, compound 10p was the most potent compound against AChE and compound 10f was the most potent compound against BChE. In vitro kinetic study demonstrated that compounds 10p and 10f were competitive inhibitors against AChE and BChE, respectively. Both these compounds had a 4-CF3 substituent on phenyl ring of benzyl pyridinium moiety. Docking study on compounds 10p and 10f demonstrated that these compounds with favorable binding energies in comparison to tacrine attached to the active sites of AChE and BChE. Molecular dynamics simulations were performed on the 10p-AChE and 10f-BChE complexes to gain deeper insights into the behavior of these compounds in the active sites of target enzymes.
dc.description.sponsorshipTehran University of Medical Sciences [1403-3-221-73931]
dc.description.sponsorshipThis work was financially supported by the Tehran University of Medical Sciences with grant number of 1403-3-221-73931.
dc.identifier.doi10.1016/j.ijbiomac.2025.145731
dc.identifier.issn0141-8130
dc.identifier.issn1879-0003
dc.identifier.pmid40617434
dc.identifier.scopus2-s2.0-105009893087
dc.identifier.scopusqualityQ1
dc.identifier.urihttps://doi.org/10.1016/j.ijbiomac.2025.145731
dc.identifier.urihttps://hdl.handle.net/11616/109585
dc.identifier.volume320
dc.identifier.wosWOS:001536833700001
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherElsevier
dc.relation.ispartofInternational Journal of Biological Macromolecules
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.snmzKA_WOS_20250329
dc.subjectAlzheimer's disease
dc.subjectBChE
dc.subjectAChE
dc.subjectRhodanine
dc.subjectAcetamide
dc.subjectBenzyl pyridinium
dc.titleRhodanine-pyridinium derivatives as a new category of cholinesterase inhibitors: Design, synthesis, in vitro and in silico enzymatic evaluations
dc.typeArticle

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