New Uses for Old Drugs: Attempts to Convert Quinolone Antibacterials into Potential Anticancer Agents Containing Ruthenium

Continuing the study of the physicochemical
and biological properties of ruthenium-quinolone adducts, four novel
complexes with the general formula [Ru([9]­aneS3)­(dmso-κS)­(quinolonato-κ2O,O)]­(PF6), containing the quinolones
levofloxacin (1), nalidixic acid (2), oxolinic
acid (3), and cinoxacin (4), were prepared
and characterized in solid state as well as in solution. Contrary
to their organoruthenium analogues, these complexes are generally
relatively stable in aqueous solution as substitution of the dimethylsulfoxide
(dmso) ligand is slow and not quantitative, and a minor release of
the quinolonato ligand is observed only in the case of 4. The complexes bind to serum proteins displaying relatively high
binding constants. DNA binding was studied using UV–vis spectroscopy,
cyclic voltammetry, and performing viscosity measurements of CT DNA
solutions in the presence of complexes 1–4. These experiments show that the ruthenium complexes interact
with DNA via intercalation. Possible electrostatic interactions occur
in the case of compound 4, which also shows the most
pronounced rate of hydrolysis. Compounds 2 and 4 also exhibit a weak inhibition of cathepsins B and S, which
are involved in the progression of a number of diseases, including
cancer. Furthermore, complex 2 displayed moderate cytotoxicity
when tested on the HeLa cell line.