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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 |
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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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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</creator><creatorcontrib>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</creatorcontrib><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. 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Javier</au><au>Di Pietro, Ornella</au><au>Espargaró Colomé, Alba</au><au>Vallverdú i Queralt, Anna</au><au>Galdeano Cantador, Carlos</au><au>Ragusa, Ilaria M</au><au>Viayna, Elisabet</au><au>Guillou, Catherine</au><au>Clos Guillén, M. Victòria</au><au>Pérez Fernández, Belén</au><au>Sabaté Lagunas, Raimon</au><au>Lamuela Raventós, Rosa Ma</au><au>Luque Garriga, F. Xavier</au><au>Muñoz-Torrero López-Ibarra, Diego</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Shogaol-huprine hybrids: Dual antioxidant and anticholinesterase agents with beta-amyloid and tau anti-aggregating properties</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><date>2014-10-01</date><risdate>2014</risdate><issn>0968-0896</issn><abstract>Multitarget compounds are increasingly being pursued for the effective treatment of complex diseases. 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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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