Browsing by Author "Murray, Ana P."

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    Dual cholinesterase inhibition by lactam-1,2,3-triazole hybrids: A click chemistry approach for drug discovery
    (2025) Cavallaro, Valeria; Bjerg, Esteban E.; Rojas, Maximiliano; Santana Romo, Fabián Mauricio; Murray, Ana P.; Radivoy, Gabriel; Duarte, Yorley; Zacconi, Flavia Cristina Milagro; Moglie, Yanina
    The 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.