Indoles and 1-(3-(benzyloxy)benzyl)piperazines: Reversible and selective monoamine oxidase B inhibitors identified by screening an in-house compound library.
Bioorg Chem
; 119: 105581, 2022 02.
Article
em En
| MEDLINE
| ID: mdl-34990933
ABSTRACT
The therapeutic indications for monoamine oxidases A and B (MAO-A and MAO-B) inhibitors that have emerged from biological studies on animal and cellular models of neurological and oncological diseases have focused drug discovery projects upon identifying reversible MAO inhibitors. Screening of our in-house academic compound library identified two hit compounds that inhibit MAO-B with IC50 values in micromolar range. Two series of indole (23 analogues) and 3-(benzyloxy)benzyl)piperazine (16 analogues) MAO-B inhibitors were derived from hits, and screened for their structure-activity relationships. Both series yielded low micromolar selective inhibitors of human MAO-B, namely indole 2 (IC50 = 12.63 ± 1.21 µM) and piperazine 39 (IC50 = 19.25 ± 4.89 µM), which is comparable to selective MAO-B inhibitor isatin (IC50 = 6.10 ± 2.81 µM), yet less potent in comparison to safinamide (IC50 = 0.029 ± 0.002 µM). Selective MAO-B inhibitors 2, 14, 38 and 39 exhibited favourable permeation of the blood-brain barrier and low cytotoxicity in the human neuroblastoma cell line SH-SY5Y.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperazina
/
Indóis
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Monoaminoxidase
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Inibidores da Monoaminoxidase
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Antineoplásicos
Tipo de estudo:
Diagnostic_studies
/
Screening_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Bioorg Chem
Ano de publicação:
2022
Tipo de documento:
Article