Discovery, synthesis, biological evaluation and molecular docking study of (R)-5-methylmellein and its analogs as selective monoamine oxidase A inhibitors.
Bioorg Med Chem
; 27(10): 2027-2040, 2019 05 15.
Article
en En
| MEDLINE
| ID: mdl-30975503
ABSTRACT
(R)-5-Methylmellein (5-MM), the major ingredient in the fermented mycelia of the medicinal fungus Xylaria nigripes (called Wuling Shen in Chinese)¸ was found to be a selective inhibitor against monoamine oxidase A (MAO-A) and might play an important role in the clinical usage of this edible fungus as an anti-depressive traditional Chinese medicine (TCM). Based on the discovery and hypothesis, a variety of (R)-5-MM analogs were synthesized and evaluated in vitro against two monoamine oxidase isoforms (MAO-A and MAO-B). Most synthetic analogs showed selective inhibition of MAO-A with IC50 values ranging from 0.06 to 29⯵M, and compound 13aR is the most potent analog with high selectivity (IC50, MAO-A 0.06⯵M; MAO-B >50⯵M). Interestingly, the enzyme kinetics study of 13aR indicated that this ligand seemed to bind in the MAO-A active site according to so-called "tight-binding inhibition" mode. The molecular docking study of 13aR was thereafter performed in order to rationalize the obtained biological results.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Isocumarinas
/
Monoaminooxidasa
/
Inhibidores de la Monoaminooxidasa
Tipo de estudio:
Diagnostic_studies
Idioma:
En
Revista:
Bioorg Med Chem
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article
País de afiliación:
China