Peptidomimetic 2-cyanopyrrolidines as potent selective cathepsin L inhibitors.
J Enzyme Inhib Med Chem
; 23(2): 190-7, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18343903
ABSTRACT
Cathepsins have been found to have important physiological roles. The implication of cathepsin L in various types of cancers is well established. In a search for selective cathepsin L inhibitors as anticancer agents, a series of 2-cyanoprrolidine peptidomimetics, carrying a nitrile group as warhead, were designed. Two series of compounds, one with a benzyl moiety and a second with an isobutyl moiety at P(2) position of the enzyme were synthesized. The synthesized compounds were evaluated for inhibitory activity against human cathepsin L and cathepsin B. Although, none of the compounds showed promising inhibitory activity, (E)N-{(S)1-[(S)2-cyano-1-pyrrolidinecarbonyl]-3-methylbutyl}-2,3-diphenylacrylamide (24) with an isobutyl moiety at P(2) was found to show selectivity as a cathepsin L inhibitor (Ki 5.3 microM for cathepsin L and Ki > 100 microM for cathepsin B). This compound could act as a new lead for the further development of improved inhibitors within this inhibitor type.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Peptídeos
/
Pirrolidinas
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Catepsinas
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Inibidores de Cisteína Proteinase
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Cianetos
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Materiais Biomiméticos
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article