Brocos-Mosquera, Iria

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  • Brocos-Mosquera, Iria (4)

Author's Bibliography

Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease

Bagán, Andrea; Rodriguez-Arévalo, Sergio; Taboada-Jara, Teresa; Griñán-Ferré, Christian; Pallàs, Mercè; Brocos-Mosquera, Iria; Callado, Luis F.; Morales-García, José A.; Pérez, Belén; Diaz, Caridad; Fernández-Godino, Rosario; Genilloud, Olga; Beljkaš, Milan; Oljačić, Slavica; Nikolić, Katarina; Escolano, Carmen

(MDPI, 2023)

TY  - JOUR
AU  - Bagán, Andrea
AU  - Rodriguez-Arévalo, Sergio
AU  - Taboada-Jara, Teresa
AU  - Griñán-Ferré, Christian
AU  - Pallàs, Mercè
AU  - Brocos-Mosquera, Iria
AU  - Callado, Luis F.
AU  - Morales-García, José A.
AU  - Pérez, Belén
AU  - Diaz, Caridad
AU  - Fernández-Godino, Rosario
AU  - Genilloud, Olga
AU  - Beljkaš, Milan
AU  - Oljačić, Slavica
AU  - Nikolić, Katarina
AU  - Escolano, Carmen
PY  - 2023
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5206
AB  - Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer’s disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I2-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I2-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I2-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson’s disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I2-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration.
PB  - MDPI
T2  - Pharmaceutics
T1  - Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease
VL  - 15
IS  - 10
DO  - 10.3390/pharmaceutics15102381
ER  - 
@article{
author = "Bagán, Andrea and Rodriguez-Arévalo, Sergio and Taboada-Jara, Teresa and Griñán-Ferré, Christian and Pallàs, Mercè and Brocos-Mosquera, Iria and Callado, Luis F. and Morales-García, José A. and Pérez, Belén and Diaz, Caridad and Fernández-Godino, Rosario and Genilloud, Olga and Beljkaš, Milan and Oljačić, Slavica and Nikolić, Katarina and Escolano, Carmen",
year = "2023",
abstract = "Humanity is facing a vast prevalence of neurodegenerative diseases, with Alzheimer’s disease (AD) being the most dominant, without efficacious drugs, and with only a few therapeutic targets identified. In this scenario, we aim to find molecular entities that modulate imidazoline I2 receptors (I2-IRs) that have been pointed out as relevant targets in AD. In this work, we explored structural modifications of well-established I2-IR ligands, giving access to derivatives with an imidazole-linked heterocycle as a common key feature. We report the synthesis, the affinity in human I2-IRs, the brain penetration capabilities, the in silico ADMET studies, and the three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of this new bunch of I2-IR ligands. Selected compounds showed neuroprotective properties and beneficial effects in an in vitro model of Parkinson’s disease, rescued the human dopaminergic cell line SH-SY5Y from death after treatment with 6-hydroxydopamine, and showed crucial anti-inflammatory effects in a cellular model of neuroinflammation. After a preliminary pharmacokinetic study, we explored the action of our representative 2-(benzo[b]thiophen-2-yl)-1H-imidazole LSL33 in a mouse model of AD (5xFAD). Oral administration of LSL33 at 2 mg/Kg for 4 weeks ameliorated 5XFAD cognitive impairment and synaptic plasticity, as well as reduced neuroinflammation markers. In summary, this new I2-IR ligand that promoted beneficial effects in a well-established AD mouse model should be considered a promising therapeutic strategy for neurodegeneration.",
publisher = "MDPI",
journal = "Pharmaceutics",
title = "Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease",
volume = "15",
number = "10",
doi = "10.3390/pharmaceutics15102381"
}
Bagán, A., Rodriguez-Arévalo, S., Taboada-Jara, T., Griñán-Ferré, C., Pallàs, M., Brocos-Mosquera, I., Callado, L. F., Morales-García, J. A., Pérez, B., Diaz, C., Fernández-Godino, R., Genilloud, O., Beljkaš, M., Oljačić, S., Nikolić, K.,& Escolano, C.. (2023). Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease. in Pharmaceutics
MDPI., 15(10).
https://doi.org/10.3390/pharmaceutics15102381
Bagán A, Rodriguez-Arévalo S, Taboada-Jara T, Griñán-Ferré C, Pallàs M, Brocos-Mosquera I, Callado LF, Morales-García JA, Pérez B, Diaz C, Fernández-Godino R, Genilloud O, Beljkaš M, Oljačić S, Nikolić K, Escolano C. Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease. in Pharmaceutics. 2023;15(10).
doi:10.3390/pharmaceutics15102381 .
Bagán, Andrea, Rodriguez-Arévalo, Sergio, Taboada-Jara, Teresa, Griñán-Ferré, Christian, Pallàs, Mercè, Brocos-Mosquera, Iria, Callado, Luis F., Morales-García, José A., Pérez, Belén, Diaz, Caridad, Fernández-Godino, Rosario, Genilloud, Olga, Beljkaš, Milan, Oljačić, Slavica, Nikolić, Katarina, Escolano, Carmen, "Preclinical Evaluation of an Imidazole-Linked Heterocycle for Alzheimer’s Disease" in Pharmaceutics, 15, no. 10 (2023),
https://doi.org/10.3390/pharmaceutics15102381 . .
7

A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration

Escolano, Carmen; Abas, Sonia; Rodriguez-Arevalo, Sergio; Bagan, Andrea; Griñan-Ferre, Christian; Vasilopoulou, Fotini; Pallas, Merce; Perez Lozano, Pilar; Brocos-Mosquera, Iria; Muguruza Carolina; Callado, Luis; Perez, Belen; Brea, Jose; Loza, M; Hernandez-Hernandez, Elena; Garcia-Sevilla, Jesus; Garcia-Fuster, M; Radan, Milica; Nikolić, Katarina; Đikić, Teodora; Diaz, Caridad; Jose Perez del Palacio; Ramos, Carmen; Vicente, Francisca; Molins, Elies

(Wiley, 2021)

TY  - CONF
AU  - Escolano, Carmen
AU  - Abas, Sonia
AU  - Rodriguez-Arevalo, Sergio
AU  - Bagan, Andrea
AU  - Griñan-Ferre, Christian
AU  - Vasilopoulou, Fotini
AU  - Pallas, Merce
AU  - Perez Lozano, Pilar
AU  - Brocos-Mosquera, Iria
AU  - Muguruza Carolina
AU  - Callado, Luis
AU  - Perez, Belen
AU  - Brea, Jose
AU  - Loza, M
AU  - Hernandez-Hernandez, Elena
AU  - Garcia-Sevilla, Jesus
AU  - Garcia-Fuster, M
AU  - Radan, Milica
AU  - Nikolić, Katarina
AU  - Đikić, Teodora
AU  - Diaz, Caridad
AU  - Jose Perez del Palacio
AU  - Ramos, Carmen
AU  - Vicente, Francisca
AU  - Molins, Elies
PY  - 2021
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4859
PB  - Wiley
C3  - The FASEB Journal
T1  - A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration
VL  - 35
IS  - S1
DO  - 10.1096/fasebj.2021.35.S1.04974
ER  - 
@conference{
author = "Escolano, Carmen and Abas, Sonia and Rodriguez-Arevalo, Sergio and Bagan, Andrea and Griñan-Ferre, Christian and Vasilopoulou, Fotini and Pallas, Merce and Perez Lozano, Pilar and Brocos-Mosquera, Iria and Muguruza Carolina and Callado, Luis and Perez, Belen and Brea, Jose and Loza, M and Hernandez-Hernandez, Elena and Garcia-Sevilla, Jesus and Garcia-Fuster, M and Radan, Milica and Nikolić, Katarina and Đikić, Teodora and Diaz, Caridad and Jose Perez del Palacio and Ramos, Carmen and Vicente, Francisca and Molins, Elies",
year = "2021",
publisher = "Wiley",
journal = "The FASEB Journal",
title = "A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration",
volume = "35",
number = "S1",
doi = "10.1096/fasebj.2021.35.S1.04974"
}
Escolano, C., Abas, S., Rodriguez-Arevalo, S., Bagan, A., Griñan-Ferre, C., Vasilopoulou, F., Pallas, M., Perez Lozano, P., Brocos-Mosquera, I., Muguruza Carolina, Callado, L., Perez, B., Brea, J., Loza, M., Hernandez-Hernandez, E., Garcia-Sevilla, J., Garcia-Fuster, M., Radan, M., Nikolić, K., Đikić, T., Diaz, C., Jose Perez del Palacio, Ramos, C., Vicente, F.,& Molins, E.. (2021). A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration. in The FASEB Journal
Wiley., 35(S1).
https://doi.org/10.1096/fasebj.2021.35.S1.04974
Escolano C, Abas S, Rodriguez-Arevalo S, Bagan A, Griñan-Ferre C, Vasilopoulou F, Pallas M, Perez Lozano P, Brocos-Mosquera I, Muguruza Carolina, Callado L, Perez B, Brea J, Loza M, Hernandez-Hernandez E, Garcia-Sevilla J, Garcia-Fuster M, Radan M, Nikolić K, Đikić T, Diaz C, Jose Perez del Palacio, Ramos C, Vicente F, Molins E. A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration. in The FASEB Journal. 2021;35(S1).
doi:10.1096/fasebj.2021.35.S1.04974 .
Escolano, Carmen, Abas, Sonia, Rodriguez-Arevalo, Sergio, Bagan, Andrea, Griñan-Ferre, Christian, Vasilopoulou, Fotini, Pallas, Merce, Perez Lozano, Pilar, Brocos-Mosquera, Iria, Muguruza Carolina, Callado, Luis, Perez, Belen, Brea, Jose, Loza, M, Hernandez-Hernandez, Elena, Garcia-Sevilla, Jesus, Garcia-Fuster, M, Radan, Milica, Nikolić, Katarina, Đikić, Teodora, Diaz, Caridad, Jose Perez del Palacio, Ramos, Carmen, Vicente, Francisca, Molins, Elies, "A bicyclic α‑iminophosphonate improves cognitive decline in 5xFAD murine model of neurodegeneration" in The FASEB Journal, 35, no. S1 (2021),
https://doi.org/10.1096/fasebj.2021.35.S1.04974 . .

Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (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

(American Chemical Society, 2020)

TY  - 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/123456789/3768
AB  - Page 3630. The affiliation of the following authors needs to be corrected. Iria Brocos-Mosquera is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Carolina Muguruza is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Luis F. Callado is affiliated with Department of Pharmacology, University of the Basque Country, UPV/EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain.
PB  - American Chemical Society
T2  - Journal of Medicinal Chemistry
T1  - Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080)
VL  - 63
IS  - 18
SP  - 10529
DO  - 10.1021/acs.jmedchem.0c01324
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 = "Page 3630. The affiliation of the following authors needs to be corrected. Iria Brocos-Mosquera is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Carolina Muguruza is affiliated with Department of Pharmacology, University of the Basque Country, UPV/ EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain. Luis F. Callado is affiliated with Department of Pharmacology, University of the Basque Country, UPV/EHU, E-48940 Leioa, Bizkaia, Spain, and Centro de Investigacioìn Biomeìdica en Red de Salud Mental, CIBERSAM, Spain.",
publisher = "American Chemical Society",
journal = "Journal of Medicinal Chemistry",
title = "Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080)",
volume = "63",
number = "18",
pages = "10529",
doi = "10.1021/acs.jmedchem.0c01324"
}
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). Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080). in Journal of Medicinal Chemistry
American Chemical Society., 63(18), 10529.
https://doi.org/10.1021/acs.jmedchem.0c01324
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. Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080). in Journal of Medicinal Chemistry. 2020;63(18):10529.
doi:10.1021/acs.jmedchem.0c01324 .
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, "Erratum: Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2Receptor Ligands for Alzheimer's Disease (Journal of Medicinal Chemistry (2020) 63:7 (3610−3633) DOI: 10.1021/acs.jmedchem.9b02080)" in Journal of Medicinal Chemistry, 63, no. 18 (2020):10529,
https://doi.org/10.1021/acs.jmedchem.0c01324 . .
15

Bicyclic α-Iminophosphonates as High Affinity Imidazoline I2 Receptor Ligands for Alzheimer's Disease

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

(American Chemical Society, 2020)

TY  - 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 . .
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