Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease
Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffered from neurodegenerative disorders, are orphan from the structural point of view and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthes...
| Authors: | ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; |
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| Format: | Article |
| Status: | Accepted version |
| Publication date: | 2020 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:2445/172618 |
| Online Access: | https://hdl.handle.net/2445/172618 |
| Access Level: | Open access |
| Keyword: | Malaltia d'Alzheimer Malalties neurodegeneratives Envelliment Alzheimer's disease Neurodegenerative Diseases Aging |
| _version_ | 1878738126098137088 |
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| author | Abás Prades, Sònia |
| author2 | Rodríguez-Arévalo, Sergio Bagan Polonio, Andrea Griñán Ferré, Christian Vasilopoulou, Foteini Brocos-Mosquera, Iria Muguruza, Carolina Pérez, Belén Molins i Grau, Elies Luque Garriga, F. Xavier Pérez Lozano, Pilar Jonghe, Steven de Daelemans, Dirk Naesens, Lieve Brea, José Loza, María Isabel Hernández-Hernández, Elena García-Sevilla, Jesús A. García-Fuster, M. Julia Radan, Milica Djikic, Teodora Nikolic, Katarina Pallàs i Llibería, Mercè, 1964- Callado, Luis F. Escolano Mirón, Carmen |
| author2_role | author author author author author author author author author author author author author author author author author author author author author author author author |
| author_browse | Abás Prades, Sònia Bagan Polonio, Andrea Brea, José Brocos-Mosquera, Iria Callado, Luis F. Daelemans, Dirk Djikic, Teodora Escolano Mirón, Carmen García-Fuster, M. Julia García-Sevilla, Jesús A. Griñán Ferré, Christian Hernández-Hernández, Elena Jonghe, Steven de Loza, María Isabel Luque Garriga, F. Xavier Molins i Grau, Elies Muguruza, Carolina Naesens, Lieve Nikolic, Katarina Pallàs i Llibería, Mercè, 1964- Pérez Lozano, Pilar Pérez, Belén Radan, Milica Rodríguez-Arévalo, Sergio Vasilopoulou, Foteini |
| author_facet | Abás Prades, Sònia Rodríguez-Arévalo, Sergio Bagan Polonio, Andrea Griñán Ferré, Christian Vasilopoulou, Foteini Brocos-Mosquera, Iria Muguruza, Carolina Pérez, Belén Molins i Grau, Elies Luque Garriga, F. Xavier Pérez Lozano, Pilar Jonghe, Steven de Daelemans, Dirk Naesens, Lieve Brea, José Loza, María Isabel Hernández-Hernández, Elena García-Sevilla, Jesús A. García-Fuster, M. Julia Radan, Milica Djikic, Teodora Nikolic, Katarina Pallàs i Llibería, Mercè, 1964- Callado, Luis F. Escolano Mirón, Carmen |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffered from neurodegenerative disorders, are orphan from the structural point of view and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and 3D-QSAR studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased the FADD protein in the hippocampus, a key marker in neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_aa09b2fa18fa435a67d03e6dec57830f |
| institution | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| instname_str | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:2445/172618 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | American Chemical Society |
| publisherStr | American Chemical Society |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease Abás Prades, Sònia Rodríguez-Arévalo, Sergio Bagan Polonio, Andrea Griñán Ferré, Christian Vasilopoulou, Foteini Brocos-Mosquera, Iria Muguruza, Carolina Pérez, Belén Molins i Grau, Elies Luque Garriga, F. Xavier Pérez Lozano, Pilar Jonghe, Steven de Daelemans, Dirk Naesens, Lieve Brea, José Loza, María Isabel Hernández-Hernández, Elena García-Sevilla, Jesús A. García-Fuster, M. Julia Radan, Milica Djikic, Teodora Nikolic, Katarina Pallàs i Llibería, Mercè, 1964- Callado, Luis F. Escolano Mirón, Carmen Malaltia d'Alzheimer Malalties neurodegeneratives Envelliment Alzheimer's disease Neurodegenerative Diseases Aging Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffered from neurodegenerative disorders, are orphan from the structural point of view and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and 3D-QSAR studies of a new family of bicyclic α-iminophosphonates endowed with relevant affinities for human brain I2-IR. Acute treatment in mice with a selected compound significantly decreased the FADD protein in the hippocampus, a key marker in neuroprotective actions. Additionally, in vivo studies in the familial Alzheimer's disease 5xFAD murine model revealed beneficial effects in behavior and cognition. These results are supported by changes in molecular pathways related to cognitive decline and Alzheimer's disease. Therefore bicyclic α-iminophosphonates are tools that may open new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions. American Chemical Society https://hdl.handle.net/2445/172618 |
| spellingShingle | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease Abás Prades, Sònia Malaltia d'Alzheimer Malalties neurodegeneratives Envelliment Alzheimer's disease Neurodegenerative Diseases Aging |
| status_str | acceptedVersion |
| title | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease |
| title_full | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease |
| title_fullStr | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease |
| title_full_unstemmed | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease |
| title_short | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease |
| title_sort | Bicyclic alfa-iminophosphonates as high affinity imidazoline I2 receptor ligands for Alzheimer's disease |
| topic | Malaltia d'Alzheimer Malalties neurodegeneratives Envelliment Alzheimer's disease Neurodegenerative Diseases Aging |
| topic_facet | Malaltia d'Alzheimer Malalties neurodegeneratives Envelliment Alzheimer's disease Neurodegenerative Diseases Aging |
| url | https://hdl.handle.net/2445/172618 |