The First Metal-Based Paullone Derivative with High Antiproliferative Activity in Vitro

9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, kenpaullone, which displays similarities in the
activity profile to flavopiridol, was modified by chemical transformations
at the lactam unit to provide a peripheral binding site able to accommodate
metal ions. The first metal-based paullone has been prepared and characterized
by single-crystal X-ray diffraction methods, solid-state cross-polarization
magic angle spinning 13C NMR spectroscopy, electrospray
ionization mass spectra, and electronic spectra. The gallium complex
[GaL2]Cl·2.5H2O, the metal-free ligand
(HL), and the starting compound used for the preparation of HL were
assessed in vitro for their cytotoxicity in a panel of human tumor
cell lines. The gallium complex was found to be 1.5−18-fold
more cytotoxic than HL, with an average IC50 value of 2.0
μM.