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

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 shogaolhuprine hybrids, purported to hit several key targets involved in Alzheimer"s disease. The hybrids have been tested in vi...

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Published in:Bioorganic & medicinal chemistry 2014-10
Main Authors: Pérez-Areales, F. Javier, Di Pietro, Ornella, Espargaró Colomé, Alba, Vallverdú i Queralt, Anna, Galdeano Cantador, Carlos, Ragusa, Ilaria M, Viayna, Elisabet, Guillou, Catherine, Clos Guillén, M. Victòria, Pérez Fernández, Belén, Sabaté Lagunas, Raimon, Lamuela Raventós, Rosa Ma, Luque Garriga, F. Xavier, Muñoz-Torrero López-Ibarra, Diego
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container_title Bioorganic & medicinal chemistry
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creator Pérez-Areales, F. Javier
Di Pietro, Ornella
Espargaró Colomé, Alba
Vallverdú i Queralt, Anna
Galdeano Cantador, Carlos
Ragusa, Ilaria M
Viayna, Elisabet
Guillou, Catherine
Clos Guillén, M. Victòria
Pérez Fernández, Belén
Sabaté Lagunas, Raimon
Lamuela Raventós, Rosa Ma
Luque Garriga, F. Xavier
Muñoz-Torrero López-Ibarra, Diego
description 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 shogaolhuprine 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 shogaolhuprine hybrids emerge as interesting brain permeable multitarget anti-Alzheimer leads.
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subjects Alzheimer's disease
Antioxidants
Disseny de medicaments
Drug design
Enzyme inhibitors
Inhibidors enzimàtics
Malaltia d'Alzheimer
Peptides
Pèptids
title Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties
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