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Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders
Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348017/ https://www.ncbi.nlm.nih.gov/pubmed/34361702 http://dx.doi.org/10.3390/molecules26154550 |
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author | Quezada, Elías Rodríguez-Enríquez, Fernanda Laguna, Reyes Cutrín, Elena Otero, Francisco Uriarte, Eugenio Viña, Dolores |
author_facet | Quezada, Elías Rodríguez-Enríquez, Fernanda Laguna, Reyes Cutrín, Elena Otero, Francisco Uriarte, Eugenio Viña, Dolores |
author_sort | Quezada, Elías |
collection | PubMed |
description | Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin–coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11–18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H(2)O(2) in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained. |
format | Online Article Text |
id | pubmed-8348017 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83480172021-08-08 Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders Quezada, Elías Rodríguez-Enríquez, Fernanda Laguna, Reyes Cutrín, Elena Otero, Francisco Uriarte, Eugenio Viña, Dolores Molecules Article Neurodegenerative diseases have a complex nature which highlights the need for multitarget ligands to address the complementary pathways involved in these diseases. Over the last decade, many innovative curcumin-based compounds have been designed and synthesized, searching for new derivatives having anti-amyloidogenic, inhibitory of tau formation, as well as anti-neuroinflammation, antioxidative, and AChE inhibitory activities. Regarding our experience studying 3-substituted coumarins with interesting properties for neurodegenerative diseases, our aim was to synthesize a new series of curcumin–coumarin hybrid analogues and evaluate their activity. Most of the 3-(7-phenyl-3,5-dioxohepta-1,6-dien-1-yl)coumarin derivatives 11–18 resulted in moderated inhibitors of hMAO isoforms and AChE and BuChE activity. Some of them are also capable of scavenger the free radical DPPH. Furthermore, compounds 14 and 16 showed neuroprotective activity against H(2)O(2) in SH-SY5Y cell line. Nanoparticles formulation of these derivatives improved this property increasing the neuroprotective activity to the nanomolar range. Results suggest that by modulating the substitution pattern on both coumarin moiety and phenyl ring, ChE and MAO-targeted derivatives or derivatives with activity in cell-based phenotypic assays can be obtained. MDPI 2021-07-28 /pmc/articles/PMC8348017/ /pubmed/34361702 http://dx.doi.org/10.3390/molecules26154550 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Quezada, Elías Rodríguez-Enríquez, Fernanda Laguna, Reyes Cutrín, Elena Otero, Francisco Uriarte, Eugenio Viña, Dolores Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders |
title | Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders |
title_full | Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders |
title_fullStr | Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders |
title_full_unstemmed | Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders |
title_short | Curcumin–Coumarin Hybrid Analogues as Multitarget Agents in Neurodegenerative Disorders |
title_sort | curcumin–coumarin hybrid analogues as multitarget agents in neurodegenerative disorders |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348017/ https://www.ncbi.nlm.nih.gov/pubmed/34361702 http://dx.doi.org/10.3390/molecules26154550 |
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