title: Targeting integrins αvβ3 and α5β1 with new β-lactam derivatives.
abstract: The αvβ3 and α5β1 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 (EC50 of 11 nM).
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy. Electronic address: paola.galletti@unibo.it.
authors: Paola
authors: P
authors: Galletti
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors: Roberto
authors: R
authors: Soldati
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors: Matteo
authors: M
authors: Pori
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors: Margherita
authors: M
authors: Durso
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors: Alessandra
authors: A
authors: Tolomelli
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy.
authors: Luca
authors: L
authors: Gentilucci
authors: Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors: Samantha Deianira
authors: SD
authors: Dattoli
authors: Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy.
authors: Monica
authors: M
authors: Baiula
authors: Department of Pharmacy and Biotechnology, University of Bologna, Via Irnerio 48, 40126 Bologna, Italy. Electronic address: santi.spampinato@unibo.it.
authors: Santi
authors: S
authors: Spampinato
authors: Department of Chemistry "G. Ciamician", University of Bologna, Via Selmi 2, 40126 Bologna, Italy. Electronic address: daria.giacomini@unibo.it.
authors: Daria
authors: D
authors: Giacomini
mesh_terms: D001384:Azetidines / Q000737:chemistry; D045744:Cell Line, Tumor; D015195:Drug Design; D006801:Humans; D039081:Integrin alpha5beta1 / Q000819:agonists / Q000378:metabolism*; D039302:Integrin alphaVbeta3 / Q000819:agonists / Q000378:metabolism*; D008024:Ligands; D058990:Molecular Targeted Therapy; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C116379:2-azetidinone; D001384:Azetidines; D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D008024:Ligands; D047090:beta-Lactams
keywords: Agonists; Azetidinones; Cell adhesion; Integrins; Lactams; Peptidomimetics