Rhamnocitrin isolated from Prunus padus var. seoulensis: A potent and selective reversible inhibitor of human monoamine oxidase A.
Bioorg Chem
; 83: 317-325, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30396116
ABSTRACT
Three flavanones and two flavones were isolated from the leaves of Prunus padus var. seoulensis by the activity-guided screening for new monoamine oxidase (MAO) inhibitors. Among the compounds isolated, rhamnocitrin (5) was found to potently and selectively inhibit human MAO-A (hMAO-A, IC50â¯=â¯0.051⯵M) and effectively inhibit hMAO-B (IC50â¯=â¯2.97⯵M). The IC50 value of 5 for hMAO-A was the lowest amongst all natural flavonoids reported to date, and the potency was 20.2 times higher than that of toloxatone (1.03⯵M), a marketed drug. In addition, 5 reversibly and competitively inhibited hMAO-A and hMAO-B with Ki values of 0.030 and 0.91⯵M, respectively. Genkwanin (4) was also observed to strongly inhibit hMAO-A and hMAO-B (IC50â¯=â¯0.14 and 0.35⯵M, respectively), and competitively inhibit hMAO-A and hMAO-B (Kiâ¯=â¯0.097 and 0.12⯵M, respectively). Molecular docking simulation reveals that the binding affinity of 5 with hMAO-A (-18.49â¯kcal/mol) is higher than that observed with hMAO-B (0.19â¯kcal/mol). Compound 5 interacts with hMAO-A at four possible residues (Asn181, Gln215, Thr336, and Tyr444), while hMAO-B forms a single hydrogen bond at Glu84. These findings suggest that compound 5 as well as 4 can be considered as novel potent and reversible hMAO-A and/or hMAO-B inhibitors or useful lead compounds for future development of hMAO inhibitors in neurological disorder therapies.
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01-internacional
Base de dados:
MEDLINE
Assunto principal:
Prunus
/
Quempferóis
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Inibidores da Monoaminoxidase
Limite:
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2019
Tipo de documento:
Article