Synthesis and biological evaluation of non-peptide alpha(v)beta(3)/alpha(5)beta(1) integrin dual antagonists containing 5,6-dihydropyridin-2-one scaffolds.
Small constrained non-peptidic molecules consisting of a polyfunctionalized rigid core, carrying appendages corresponding to arginine and aspartic acid side chains, have been recently reported to be promising for drug development. In this work, the 5,6-dihydropyridin-2-one was envisaged as a scaffold to turn into potential integrin ligands, introducing a carboxylic acid and a basic appendage. The synthesis and the antiadhesion activity of a small library of peptidomimetics capable to recognize alpha(v)beta(3) and alpha(5)beta(1) integrins has been herein reported.
Benfatti
Fides
F
Dipartimento di Chimica "G. Ciamician", Università di Bologna, Via Selmi 2, 40126 Bologna, Italy.
Cardillo
Giuliana
G
Fabbroni
Serena
S
Galzerano
Patrizia
P
Gentilucci
Luca
L
Juris
Riccardo
R
Tolomelli
Alessandra
A
Baiula
Monica
M
Spartà
Antonino
A
Spampinato
Santi
S
D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D039081:Integrin alpha5beta1 / Q000037:antagonists & inhibitors*; D039302:Integrin alphaVbeta3 / Q000037:antagonists & inhibitors*; D020014:K562 Cells; D008024:Ligands; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D039081:Integrin alpha5beta1; D039302:Integrin alphaVbeta3; D008024:Ligands; D011725:Pyridines; D011728:Pyridones; D054852:Small Molecule Libraries