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 . .

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 . .