20S proteasome as novel biological target for organochalcogenanes.
Eur J Med Chem
; 73: 280-5, 2014 Feb 12.
Article
em En
| MEDLINE
| ID: mdl-24463395
A series of hypervalent selenium- and tellurium-containing compounds (organoselenuranes and organotelluranes) was evaluated aiming novel inhibitors of a threonine protease, namely the 20S proteasome (20S PT). In vitro assays demonstrated high inhibitory potency and specificity of these compounds toward the ß2 catalytic site of the 20S PT. Organotelluranes were identified as more potent inhibitors than organoselenuranes since their IC50 ranged from 3.5 to 16 µM while for organoselenuranes the IC50 ranged from 16 to 35 µM indicating great potential to be explored in 20S proteasome inhibition. Cellular assays with those compounds were employed to verify the cytotoxicity and ability to inhibit 20S proteasome in cell. These assays demonstrated that organoselenuranes are capable of maintaining their selectivity in cell while the organotelluranes became inactive under cellular conditions. Stability studies of the organochalcogenanes were performed by (77)Se and (125)Te NMR analysis. It was observed that organotelluranes are stable under enzymatic assay conditions and, organoselenuranes, the structures responsible for inhibitory activity are cyclized organoselenuranes.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
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Telúrio
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Compostos Organosselênicos
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Complexo de Endopeptidases do Proteassoma
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Inibidores de Proteassoma
Limite:
Animals
Idioma:
En
Revista:
Eur J Med Chem
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Brasil
País de publicação:
França