Phenoxypropanolamine derivatives as selective inhibitors of the 20S proteasome ß1 and ß5 subunits.
Bioorg Med Chem Lett
; 27(23): 5172-5178, 2017 12 01.
Article
em En
| MEDLINE
| ID: mdl-29113763
ABSTRACT
New series of thiophene-containing phenoxypropanolamines were synthesized and evaluated for their potency to inhibit the three proteolytic activities of the mammalian 20S proteasome. Noticeable inhibition of both ChT-L and PA activities was obtained with three compounds one with unsubstituted phenoxypropanolamine group (7) and the two others with a p-Cl-substituted group (4 and 9). For three other compounds (3, 8 and 10), ChT-L activity alone was significantly inhibited. In silico docking performed on the ß5 and ß1 subunits bearing the respective ChT-L and PA catalytic sites showed features common to poses associated with active compounds. These features may constitute a selectivity criterion for structure-guided inhibitor design.
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Base de dados:
MEDLINE
Assunto principal:
Complexo de Endopeptidases do Proteassoma
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Fenoxipropanolaminas
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Inibidores de Proteassoma
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article