Highly Antiproliferative Ruthenium(II) and Osmium(II) Arene Complexes with Paullone-Derived Ligands

The paullones are known as inhibitors of cyclin-dependent kinases and glycogen synthase kinase-3. However, their low aqueous solubility and bioavailability impeded their medicinal application. To overcome these problems, we developed paullone-based organic ligands and prepared organometallic complexes of the general formula [M II Cl(η 6 - p -cymene)HL]Cl ( 1, HL = HL 1; 2, HL = HL 2; a, M = Ru; b, M = Os). The compounds have been characterized by electrospray ionization mass spectrometry, IR, UV–vis, NMR spectroscopy, X-ray diffraction, conductivity measurements, and cyclic voltammetry. In addition, their antiproliferative activity in three human cancer cell lines has been assayed. The IC 50 values (in the submicromolar to very low micromolar concentration range) indicate their high antiproliferative activity in all three cell lines, making them potential candidates for further development as antitumor drugs. The hydrolysis behavior and reactivity of 1 and 2 toward 5′-GMP are also reported.