Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease
Само за регистроване кориснике
2020
Аутори
Abás, SòniaRodríguez-Arévalo, Sergio
Bagán, Andrea
Griñán-Ferré, Christian
Vasilopoulou, Foteini
Brocos-Mosquera, Iria
Muguruza, Carolina
Pérez, Belén
Molins, Elies
Luque, F. Javier
Pérez-Lozano, Pilar
De Jonghe, Steven
Daelemans, Dirk
Naesens, Lieve
Brea, José
Loza, M. Isabel
Hernández-Hernández, Elena
García-Sevilla, Jesús A.
García-Fuster, M. Julia
Radan, Milica
Đikić, Teodora
Nikolić, Katarina
Pallàs, Mercè
Callado, Luis F.
Escolano, Carmen
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (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 Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of 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 op...en new therapeutic avenues for I2-IR, particularly for unmet neurodegenerative conditions.
Извор:
Journal of Medicinal Chemistry, 2020, 63, 7, 3610-3633Издавач:
- American Chemical Society
Финансирање / пројекти:
- Синтеза, квантитативни однос између структуре и дејства, физичко-хемијска карактеризација и анализа фармаколошки активних супстанци (RS-MESTD-Basic Research (BR or ON)-172033)
- Ministerio de Economı́a y Competitividad of Spain(SAF2016-77703) and the Basque Government (IT1211-19)
- Spanish Ministerio de Economı́a, Industria yCompetitividad (grant MDM-2017-0767; AEI/FEDER UE),and Generalitat de Catalunya (grant 2017SGR1746)
Напомена:
- Link to erratum: https://farfar.pharmacy.bg.ac.rs/handle/123456789/3768
Повезане информације:
- Повезани садржај
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3768
DOI: 10.1021/acs.jmedchem.9b02080
ISSN: 0022-2623
WoS: 000526405300015
Scopus: 2-s2.0-85083077827
Институција/група
PharmacyTY - JOUR AU - Abás, Sònia AU - Rodríguez-Arévalo, Sergio AU - Bagán, Andrea AU - Griñán-Ferré, Christian AU - Vasilopoulou, Foteini AU - Brocos-Mosquera, Iria AU - Muguruza, Carolina AU - Pérez, Belén AU - Molins, Elies AU - Luque, F. Javier AU - Pérez-Lozano, Pilar AU - De Jonghe, Steven AU - Daelemans, Dirk AU - Naesens, Lieve AU - Brea, José AU - Loza, M. Isabel AU - Hernández-Hernández, Elena AU - García-Sevilla, Jesús A. AU - García-Fuster, M. Julia AU - Radan, Milica AU - Đikić, Teodora AU - Nikolić, Katarina AU - Pallàs, Mercè AU - Callado, Luis F. AU - Escolano, Carmen PY - 2020 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3576 AB - Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (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 Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of 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. PB - American Chemical Society T2 - Journal of Medicinal Chemistry T1 - Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease VL - 63 IS - 7 SP - 3610 EP - 3633 DO - 10.1021/acs.jmedchem.9b02080 ER -
@article{ author = "Abás, Sònia and Rodríguez-Arévalo, Sergio and Bagán, Andrea and Griñán-Ferré, Christian and Vasilopoulou, Foteini and Brocos-Mosquera, Iria and Muguruza, Carolina and Pérez, Belén and Molins, Elies and Luque, F. Javier and Pérez-Lozano, Pilar and De Jonghe, Steven and Daelemans, Dirk and Naesens, Lieve and Brea, José and Loza, M. Isabel and Hernández-Hernández, Elena and García-Sevilla, Jesús A. and García-Fuster, M. Julia and Radan, Milica and Đikić, Teodora and Nikolić, Katarina and Pallàs, Mercè and Callado, Luis F. and Escolano, Carmen", year = "2020", abstract = "Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure-activity relationship (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 Fas-associated protein with death domain (FADD) in the hippocampus, a key signaling mediator of 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.", publisher = "American Chemical Society", journal = "Journal of Medicinal Chemistry", title = "Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease", volume = "63", number = "7", pages = "3610-3633", doi = "10.1021/acs.jmedchem.9b02080" }
Abás, S., Rodríguez-Arévalo, S., Bagán, A., Griñán-Ferré, C., Vasilopoulou, F., Brocos-Mosquera, I., Muguruza, C., Pérez, B., Molins, E., Luque, F. J., Pérez-Lozano, P., De Jonghe, S., Daelemans, D., Naesens, L., Brea, J., Loza, M. I., Hernández-Hernández, E., García-Sevilla, J. A., García-Fuster, M. J., Radan, M., Đikić, T., Nikolić, K., Pallàs, M., Callado, L. F.,& Escolano, C.. (2020). Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease. in Journal of Medicinal Chemistry American Chemical Society., 63(7), 3610-3633. https://doi.org/10.1021/acs.jmedchem.9b02080
Abás S, Rodríguez-Arévalo S, Bagán A, Griñán-Ferré C, Vasilopoulou F, Brocos-Mosquera I, Muguruza C, Pérez B, Molins E, Luque FJ, Pérez-Lozano P, De Jonghe S, Daelemans D, Naesens L, Brea J, Loza MI, Hernández-Hernández E, García-Sevilla JA, García-Fuster MJ, Radan M, Đikić T, Nikolić K, Pallàs M, Callado LF, Escolano C. Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease. in Journal of Medicinal Chemistry. 2020;63(7):3610-3633. doi:10.1021/acs.jmedchem.9b02080 .
Abás, Sònia, Rodríguez-Arévalo, Sergio, Bagán, Andrea, Griñán-Ferré, Christian, Vasilopoulou, Foteini, Brocos-Mosquera, Iria, Muguruza, Carolina, Pérez, Belén, Molins, Elies, Luque, F. Javier, Pérez-Lozano, Pilar, De Jonghe, Steven, Daelemans, Dirk, Naesens, Lieve, Brea, José, Loza, M. Isabel, Hernández-Hernández, Elena, García-Sevilla, Jesús A., García-Fuster, M. Julia, Radan, Milica, Đikić, Teodora, Nikolić, Katarina, Pallàs, Mercè, Callado, Luis F., Escolano, Carmen, "Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease" in Journal of Medicinal Chemistry, 63, no. 7 (2020):3610-3633, https://doi.org/10.1021/acs.jmedchem.9b02080 . .