Osthenol, a prenylated coumarin, as a monoamine oxidase A inhibitor with high selectivity.
Bioorg Med Chem Lett
; 29(6): 839-843, 2019 03 15.
Article
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| MEDLINE
| ID: mdl-30686752
ABSTRACT
Osthenol (6), a prenylated coumarin isolated from the dried roots of Angelica pubescens, potently and selectively inhibited recombinant human monoamine oxidase-A (hMAO-A) with an IC50 value of 0.74⯵M and showed a high selectivity index (SIâ¯>â¯81.1) for hMAO-A versus hMAO-B. Compound 6 was a reversible competitive hMAO-A inhibitor (Kiâ¯=â¯0.26⯵M) with a potency greater than toloxatone (IC50â¯=â¯0.93⯵M), a marketed drug. Isopsoralen (3) and bakuchicin (1), furanocoumarin derivatives isolated from Psoralea corylifolia L., showed slightly higher IC50 values (0.88 and 1.78⯵M, respectively) for hMAO-A than 6, but had low SI values (3.1 for both). Other coumarins tested did not effectively inhibit hMAO-A or hMAO-B. A structural comparison suggested that the 8-(3,3-dimethylallyl) group of 6 increased its inhibitory activity against hMAO-A compared with the 6-methoxy group of scopoletin (4). Molecular docking simulations revealed that the binding affinity of 6 for hMAO-A (-8.5â¯kcal/mol) was greater than that for hMAO-B (-5.6â¯kcal/mol) and that of 4 for hMAO-A (-7.3â¯kcal/mol). Docking simulations also implied that 6 interacted with hMAO-A at Phe208 and with hMAO-B at Ile199 by carbon hydrogen bondings. Our findings suggest that osthenol, derived from natural products, is a selective and potent reversible inhibitor of MAO-A, and can be regarded a potential lead compound for the design of novel reversible MAO-A inhibitors.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Cumarinas
/
Monoaminooxidasa
/
Inhibidores de la Monoaminooxidasa
Límite:
Humans
Idioma:
En
Revista:
Bioorg Med Chem Lett
Asunto de la revista:
BIOQUIMICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article