Targeting integrins αvß3 and α5ß1 with new ß-lactam derivatives.
Eur J Med Chem
; 83: 284-93, 2014 Aug 18.
Article
em En
| MEDLINE
| ID: mdl-24973662
ABSTRACT
The αvß3 and α5ß1 integrins are widely expressed in different cancer types and recognize the tripeptide Arg-Gly-Asp (RGD) motif present in several extracellular matrix proteins. We report here the design, synthesis and biological activity of some new ß-lactam derivatives specifically designed to target integrins. The new molecules contain the azetidinone as the only cyclic framework armed with carboxylic acid and amine terminals spaced from 9 to 14 atoms to switch on recognition by integrins. All tested molecules showed a concentration-dependent enhancement in fibronectin-mediated adhesion of K562 and SK-MEL-24 cells; in particular 1, expressed a higher affinity towards α5ß1 integrin (EC50 of 12 nM) and 2 was more selective for integrin αvß3 (EC50 of 11 nM).
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Integrina alfa5beta1
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Integrina alfaVbeta3
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Beta-Lactamas
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Terapia de Alvo Molecular
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article