The αvβ3 and α5β 1 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 β-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 α5β1 integrin (EC50 of 12 nM) and 2 was more selective for integrin αvβ3 (EC 50 of 11 nM). © 2014 Elsevier Masson SAS. All rights reserved.

Galletti, P., Soldati, R., Pori, M., Durso, M., Tolomelli, A., Gentilucci, L., et al. (2014). Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 83, 284-293 [10.1016/j.ejmech.2014.06.041].

Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives

GALLETTI, PAOLA;SOLDATI, ROBERTO;PORI, MATTEO;DURSO, MARGHERITA;TOLOMELLI, ALESSANDRA;GENTILUCCI, LUCA;DATTOLI, SAMANTHA DEIANIRA;BAIULA, MONICA;SPAMPINATO, SANTI MARIO;GIACOMINI, DARIA
2014

Abstract

The αvβ3 and α5β 1 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 β-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 α5β1 integrin (EC50 of 12 nM) and 2 was more selective for integrin αvβ3 (EC 50 of 11 nM). © 2014 Elsevier Masson SAS. All rights reserved.
2014
Galletti, P., Soldati, R., Pori, M., Durso, M., Tolomelli, A., Gentilucci, L., et al. (2014). Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives. EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 83, 284-293 [10.1016/j.ejmech.2014.06.041].
Galletti, Paola; Soldati, Roberto; Pori, Matteo; Durso, Margherita; Tolomelli, Alessandra; Gentilucci, Luca; Dattoli, SAMANTHA DEIANIRA; Baiula, Monic...espandi
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/349520
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