Portal de investigación
Potent, selective and reversible hMAO-B inhibition by benzalphthalides: Synthesis, enzymatic and cellular evaluations and virtual docking and predictive studies
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Autores de IBSAL
Autores ajenos a IBSAL
- Barboza, B
- de la Fuente, LC
- Quezada, E
- Munin, J
- Vina, D
Grupos
Abstract
Monoaminooxidases (MAOs) are important targets for drugs used in the treatment of neurological and psychiatric disorders and particularly on Parkinson's Disease (PD). Compounds containing a trans-stilbenoid skeleton have demonstrated good selective and reversible MAO-B inhibition. Here, twenty-two (Z)-3-benzylidenephthalides (benzalphthalides, BPHs) displaying a trans-stilbenoid skeleton have been synthesised and evaluated as inhibitors of the MAO-A and MAO-B isoforms. Some BPHs have selectively inhibited MAO-B, with IC50 values ranging from sub-nM to mu M. The most potent compound with IC50 = 0.6 nM was the 3 ',4 '-dichloro-BPH 16, which showed highly selective and reversible MAO-B inhibitory activity. Furthermore, the most selective BPHs displayed a significant protection against the apoptosis, and mitochondrial toxic effects induced by 6-hydroxydopamine (6OHDA) on SH-SY5Y cells, used as a cellular model of PD. The results of virtual binding studies on the most potent compounds docked in MAO-B and MAO-A were in agreement with the potencies and selectivity indexes found experimentally. Additionally, related to toxicity risks, drug-likeness and ADME properties, the predictions found for the most relevant BPHs in this research were within those ranges established for drug candidates.
Datos de la publicación
- ISSN/ISSNe:
- 0045-2068, 1090-2120
- Tipo:
- Article
- Páginas:
- -
- PubMed:
- 38457955
BIOORGANIC CHEMISTRY ACADEMIC PRESS INC ELSEVIER SCIENCE
Citas Recibidas en Web of Science: 2
Documentos
- No hay documentos
Filiaciones
Keywords
- Benzalphthalides; Monoaminoxidase inhibitors; Selectivity; Reversibility; Cellular protection; Docking
Financiación
Proyectos asociados
3. Frailty and Aging. 3.1. Healthy aging biological mechanisms oriented to the maintenance of functional autonomy and mechanisms leading to frailty and disability. CICERFES
Investigador Principal: Juan Pedro Bolaños Hernández
CB16/10/00282 . Instituto de Salud Carlos III . 2017
Cita
del Olmo E,Barboza B,Delgado M,Escala N,Jimenez D,Lopez JL,de la Fuente LC,Quezada E,Munin J,Vina D,Bolanos JP,San Feliciano A. Potent, selective and reversible hMAO-B inhibition by benzalphthalides: Synthesis, enzymatic and cellular evaluations and virtual docking and predictive studies. BIOORG CHEM. 2024. 146. 107255. IF:4,500. (1).