Synthesis, characterization, and antitumor properties of ruthenium(II) anthraquinone complexes

Three new Ru(II) complexes, [Ru(dmb)(2)(ipad)](ClO4)(2) (dmb=4,4-dimethyl-2,2-bipyridine, ipad=2-(anthracene-9,10-dione-2-yl) imidazo[4,5-f][1,10]phenanthroline, 1), [Ru(dmp)(2)(ipad)](ClO4)(2) (dmp=2,9-dimethyl-1,10-phenanthroline, 2), and [Ru(dip)(2)(ipad)](ClO4)(2) (dip=4,7-diphenyl-1,10-phenanthroline, 3), have been synthesized and characterized. The three Ru(II) complexes intercalate with the base pairs of DNA. The in vitro antiproliferative activities and apoptosis-inducing characteristics of these complexes were investigated. The complexes exhibited cytotoxicity against various human cancer cell lines. BEL-7402 cells displayed the highest sensitivity to 1, accounted for by the greatest cellular uptake. Complex 1 was shown to accumulate preferentially in the nuclei of BEL-7402 cells and cause DNA damage and induce apoptosis, which involved cell cycle arrest and reactive oxygen species generation. [GRAPHICS]