Medicarpin and Homopterocarpin Isolated from Canavalia lineata as Potent and Competitive Reversible Inhibitors of Human Monoamine Oxidase-B.
Molecules
; 28(1)2022 Dec 28.
Article
em En
| MEDLINE
| ID: mdl-36615451
ABSTRACT
Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13. Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (Ki = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13. However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders.
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Base de dados:
MEDLINE
Assunto principal:
Inibidores da Monoaminoxidase
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Neuroblastoma
Limite:
Humans
Idioma:
En
Revista:
Molecules
Assunto da revista:
BIOLOGIA
Ano de publicação:
2022
Tipo de documento:
Article