Characterization of the anti-proliferative mechanism of action of a novel 2,3-benzodiazepine-4-one derivative (1G)

A novel 2,3-benzodiazepin-4-one non-competitive AMPA antagonist derivative, named 1G, has shown the ability to modulate the cell cycle in different cell lines in a time and dose dependent manner, causing G2/M phase arrest and inducing apoptosis. The aim of the study was to investigate the anti-proliferative mechanism of action of compound 1G and its interaction with microtubules. The results show that the molecule alters the assembly of the mitotic spindle, causing the formation of multipolar spindles in dividing cells and the activation of the Spindle Assembly Checkpoint. Further studies display that 1G is able to modulate microtubules dynamics, delaying tubulin repolymerization and quickly altering EB1 comets growth speed and lenght. Finally, our data exclude the possibility of a direct binding between tubulin and the molecule.