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Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties

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Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. Herein, we describe the design and synthesis of a novel class of shogaol
huprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vitro for their inhibitory activity against human acetylcholinesterase and butyrylcholinesterase and antioxidant activity (ABTS.+, DPPH and Folin-Ciocalteu assays), and in intact Escherichia coli cells for their Aβ42 and tau anti-aggregating activity. Also, their brain penetration has been assessed (PAMPA-BBB assay). Even though the hybrids are not as potent AChE inhibitors or antioxidant agents as the parent huprine Y and [4]-shogaol, respectively, they still exhibit very potent anticholinesterase and antioxidant activities and are much more potent Aβ42 and tau anti-aggregating agents than the parent compounds. Overall, the shogaol
huprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.

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PÉREZ AREALES, Francisco javier, DI PIETRO, O., ESPARGARÓ COLOMÉ, Alba, VALLVERDÚ I QUERALT, Anna, GALDEANO CANTADOR, Carlos, RAGUSA, Ilaria m., VIAYNA, Elisabet, GUILLOU, Catherine, CLOS, Victòria, PÉREZ FERNÁNDEZ, Belén, SABATÉ LAGUNAS, Raimon, LAMUELA RAVENTÓS, Rosa ma., LUQUE GARRIGA, F. xavier, MUÑOZ-TORRERO LÓPEZ-IBARRA, Diego. Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties. _Bioorganic & Medicinal Chemistry_. 2014. Vol. 22, núm. 19, pàgs. 5298-5307. [consulta: 8 de gener de 2026]. ISSN: 0968-0896. [Disponible a: https://hdl.handle.net/2445/59237]

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