Discovery of novel benzofuran-based compounds with neuroprotective and immunomodulatory properties for Alzheimer's disease treatment
| Autor: | Silvia Gobbi, Alessandra Bisi, Letizia Pruccoli, Manuela Bartolini, Ignacio Moraleda, Serena Montanari, Marina Naldi, Sabrina Petralla, Barbara Monti, Alessia Ligresti, Isabel Iriepa, Alessandro Rabbito, Vincenzo Di Marzo, Ali M. Mahmoud, Federica Belluti, Andrea Tarozzi, Angela Rampa |
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| Přispěvatelé: | Montanari S., Mahmoud A.M., Pruccoli L., Rabbito A., Naldi M., Petralla S., Moraleda I., Bartolini M., Monti B., Iriepa I., Belluti F., Gobbi S., Di Marzo V., Bisi A., Tarozzi A., Ligresti A., Rampa A. |
| Rok vydání: | 2019 |
| Předmět: |
Amyloid beta-Peptide
Cannabinoid receptor Pharmacology 01 natural sciences Receptor Cannabinoid CB2 Mice Immunologic Factor Peptide Fragment Receptor Cannabinoid CB1 Catalytic Domain Drug Discovery Cannabinoid receptor type 2 Cholinesterase Inhibitor Anti-inflammatory M2 phenotype Butyrylcholinesterase 0303 health sciences Chemistry CB receptor General Medicine Ligand (biochemistry) Endocannabinoid system Neuroprotection Molecular Docking Simulation Neuroprotective Agents CB receptors Acetylcholinesterase lipids (amino acids peptides and proteins) Microglia Cricetulu Alzheimer's disease Benzofuran scaffold Human Protein Binding Neuroprotective Agent CHO Cells MTDL Small Molecule Libraries 03 medical and health sciences Cricetulus Alzheimer Disease Cell Line Tumor Aβ peptide medicine Animals Humans Immunologic Factors Inverse agonist Benzofurans 030304 developmental biology Amyloid beta-Peptides Animal A beta peptide 010405 organic chemistry Organic Chemistry medicine.disease Peptide Fragments 0104 chemical sciences CHO Cell Drug Design Cholinesterase Inhibitors Benzofuran |
| Zdroj: | European journal of medicinal chemistry 178 (2019): 243–258. doi:10.1016/j.ejmech.2019.05.080 info:cnr-pdr/source/autori:Montanari, Serena; Mahmoud, Ali Mokhtar; Pruccoli, Letizia; Rabbito, Alessandro; Naldi, Marina; Petralla, Sabrina; Moraleda, Ignacio; Bartolini, Manuela; Monti, Barbara; Iriepa, Isabel; Belluti, Federica; Gobbi, Silvia; Di Marzo, Vincenzo; Bisi, Alessandra; Tarozzi, Andrea; Ligresti, Alessia; Rampa, Angela/titolo:Discovery of novel benzofuran-based compounds with neuroprotective and immunomodulatory properties for Alzheimer's disease treatment/doi:10.1016%2Fj.ejmech.2019.05.080/rivista:European journal of medicinal chemistry/anno:2019/pagina_da:243/pagina_a:258/intervallo_pagine:243–258/volume:178 European Journal of Medicinal Chemistry |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2019.05.080 |
| Popis: | To address the multifactorial nature of Alzheimer's Disease (AD), a multi-target-directed ligand approach was herein developed. As a follow-up of our previous studies, a small library of newly designed 2-arylbenzofuran derivatives was evaluated towards cholinesterases and cannabinoid receptors. The two most promising compounds, 8 and 10, were then assessed for their neuroprotective activity and for their ability to modulate the microglial phenotype. Compound 8 emerged as able to fight AD from several directions: it restored the cholinergic system by inhibiting butyrylcholinesterase, showed neuroprotective activity against A beta(1-42) oligomers, was a potent and selective CB2 ligand and had immunomodulatory effects, switching microglia from the pro-inflammatory M1 to the neuroprotective M2 phenotype. Derivative 10 was a potent CB2 inverse agonist with promising immunomodulatory properties and could be considered as a tool for investigating the role of CB2 receptors and for developing potential immunomodulating drugs addressing the endocannabinoid system. (C) 2019 Elsevier Masson SAS. All rights reserved. |
| Databáze: | OpenAIRE |
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