Dual cholinesterase inhibition by lactam-1,2,3-triazole hybrids: A click chemistry approach for drug discovery

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dc.article.number108643
dc.catalogadorjlo
dc.contributor.authorCavallaro, Valeria
dc.contributor.authorBjerg, Esteban E.
dc.contributor.authorRojas, Maximiliano
dc.contributor.authorSantana Romo, Fabián Mauricio
dc.contributor.authorMurray, Ana P.
dc.contributor.authorRadivoy, Gabriel
dc.contributor.authorDuarte, Yorley
dc.contributor.authorZacconi, Flavia Cristina Milagro
dc.contributor.authorMoglie, Yanina
dc.date.accessioned2025-11-25T19:30:23Z
dc.date.available2025-11-25T19:30:23Z
dc.date.issued2025
dc.description.abstractThe urgent need for sustainable treatments for neurodegenerative disorders has led to the development of novel cholinesterase inhibitors. In this work, sixteen lactam-1,2,3-triazole hybrids were efficiently synthesized via copper nanoparticle-catalyzed click chemistry under green conditions and without additives. Most compounds exhibited good to excellent inhibition of AChE and BChE in vitro, with compound 4 m emerging as the most potent (IC₅₀ = 0.7 μM for AChE and 0.2 μM for BChE). Molecular docking, dynamics simulations, and kinetic analyses revealed key binding interactions and identified 4 m as a mixed-type inhibitor. ADMETox predictions indicated favorable pharmacokinetic profiles, and all compounds were fully characterized using spectroscopic and HRMS techniques. This study highlights a modern, eco-friendly strategy for designing potent dual cholinesterase inhibitors with therapeutic potential for Alzheimer's disease.
dc.description.funderANID
dc.description.funderAgencia Nacional de Promoción Científica y Tecnológica
dc.description.funderAgencia Nacional de Promoción Científica y Tecnológica
dc.description.funderUniversidad Nacional del Sur
dc.description.funderUniversidad Nacional del Sur
dc.description.funderConsejo Nacional de Investigaciones Científicas y Técnicas
dc.description.funderConsejo Nacional de Investigaciones Científicas y Técnicas
dc.description.funderCONICYT FONDECYT
dc.description.funderCONICYT FONDECYT
dc.format.extent16 páginas
dc.fuente.origenSCOPUS
dc.identifier.doi10.1016/j.bioorg.2025.108643
dc.identifier.eissn1090-2120
dc.identifier.issn0045-2068
dc.identifier.scopusidSCOPUS_ID:105006992417
dc.identifier.urihttps://doi.org/10.1016/j.bioorg.2025.108643
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/107108
dc.identifier.wosidWOS:001504415400002
dc.information.autorucEscuela de Química; Santana Romo, Fabián Mauricio; 0000-0002-8753-3349; 1031362
dc.information.autorucInstituto de Ingeniería Biológica y Médica; Zacconi, Flavia Cristina Milagro; 0000-0002-3676-0453; 1011127
dc.language.isoen
dc.revistaBioorganic Chemistry
dc.subjectAcetyl and butyrylcholinesterase
dc.subjectADMETox predictions
dc.subjectClick chemistry
dc.subjectEnzymatic inhibition
dc.subjectLactams
dc.subjectMolecular docking
dc.subjectTriazoles
dc.subject.ddc510
dc.subject.ods03 Good health and well-being
dc.subject.odspa03 Salud y bienestar
dc.titleDual cholinesterase inhibition by lactam-1,2,3-triazole hybrids: A click chemistry approach for drug discovery
dc.typeartículo
dc.volumen163
sipa.codpersvinculados1031362
sipa.codpersvinculados1011127
sipa.trazabilidadSCOPUS;2025-06-15
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