Artículo
A Multitarget Approach against Neuroinflammation: Alkyl Substituted Coumarins as Inhibitors of Enzymes Involved in Neurodegeneration
Autor/es | Berrino, Emanuela
Carradori, Simone Carta, Fabrizio Melfi, Francesco Gallorini, Marialucia Poli, Giulio Fernández-Bolaños Guzmán, José María López López, Óscar Supuran, Claudiu T. |
Departamento | Universidad de Sevilla. Departamento de Química orgánica |
Fecha de publicación | 2023-11-25 |
Fecha de depósito | 2024-05-08 |
Publicado en |
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Resumen | Neurodegenerative disorders (NDs) include a large range of diseases characterized by
neural dysfunction with a multifactorial etiology. The most common NDs are Alzheimer’s disease
and Parkinson’s disease, in which ... Neurodegenerative disorders (NDs) include a large range of diseases characterized by neural dysfunction with a multifactorial etiology. The most common NDs are Alzheimer’s disease and Parkinson’s disease, in which cholinergic and dopaminergic systems are impaired, respectively. Despite different brain regions being affected, oxidative stress and inflammation were found to be common triggers in the pathogenesis and progression of both diseases. By taking advantage of a multi-target approach, in this work we explored alkyl substituted coumarins as neuroprotective agents, capable to reduce oxidative stress and inflammation by inhibiting enzymes involved in neurodegeneration, among which are Carbonic Anhydrases (CAs), Monoamine Oxidases (MAOs), and Cholinesterases (ChEs). The compounds were synthesized and profiled against the three targeted enzymes. The binding mode of the most promising compounds (7 and 9) within MAO-A and -B was analyzed through molecular modeling studies, providing and explanation for the different selectivities observed for the MAO isoforms. In vitro biological studies using LPS-stimulated rat astrocytes showed that some compounds were able to counteract the oxidative stress-induced neuroinflammation and hamper interleukin-6 secretion, confirming the success of this multitarget approach. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Agencia Estatal de Investigación. España Junta de Andalucía |
Identificador del proyecto | PID2020-116460RB-I00
FQM134 |
Cita | Berrino, E., Carradori, S., Carta, F., Melfi, F., Gallorini, M., Poli, G.,...,Supuran, C.T. (2023). A Multitarget Approach against Neuroinflammation: Alkyl Substituted Coumarins as Inhibitors of Enzymes Involved in Neurodegeneration. Antioxidants, 12 (12), 2044. https://doi.org/10.3390/antiox12122044. |
Ficheros | Tamaño | Formato | Ver | Descripción |
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antioxidants-12-02044-v2.pdf | 11.36Mb | [PDF] | Ver/ | |