title: New β-Lactam Derivatives Modulate Cell Adhesion and Signaling Mediated by RGD-Binding and Leukocyte Integrins.
abstract: A novel series of β-lactam derivatives that was designed and synthesized to target RGD-binding and leukocyte integrins is reported. The compound library was evaluated by investigating the effects on integrin-mediated cell adhesion and cell signaling in cell lines expressing αvβ3, αvβ5, αvβ6, α5β1, αIIbβ3, α4β1, and αLβ2integrins. SAR analysis of the new series of azetidinones enabled the recognition of structural elements associated with integrin selectivity. We obtained selective and potent agonists that could induce cell adhesion and promote cell signaling mediated by αvβ3, αvβ5, α5β1, or α4β1integrin, and antagonists for the integrins αvβ3and α5β1,as well as α4β1and αLβ2, preventing the effects elicited by the respective endogenous agonists.
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Baiula
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna , Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Galletti
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna , Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Martelli
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna , Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Soldati
authors.affiliation: Department of Chemistry, University of Milan , Via Golgi 19, 20133 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Belvisi
authors.affiliation: Department of Chemistry, University of Milan , Via Golgi 19, 20133 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Civera
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Samantha Deianira
authors.initials: SD
authors.lastname: Dattoli
authors.affiliation: Department of Pharmacy and Biotechnology, University of Bologna , Via Irnerio 48, 40126, Bologna, Italy.
authors.forename: Santi Mario
authors.initials: SM
authors.lastname: Spampinato
authors.affiliation: Department of Chemistry "G. Ciamician", University of Bologna , Via Selmi 2, 40126 Bologna, Italy.
authors.forename: Daria
authors.initials: D
authors.lastname: Giacomini
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D016023:Integrins / Q000819:agonists / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013329:Structure-Activity Relationship; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016023:Integrins; D009842:Oligopeptides; D047090:beta-Lactams; C047981:arginyl-glycyl-aspartic acid