Cytotoxicity, apoptosis, interaction with DNA, cellular uptake, and cell cycle arrest of ruthenium(II) polypyridyl complexes containing 4,4'-dimethyl-2,2'-bipyridine as ancillary ligand

摘要

Two new ruthenium(II) polypyridyl complexes, [Ru(dmb)_2(DNPIP)](ClO_4)2 (1) (DNPIP = 2-(2,4-dinitrophenyl)imidazo[4,5-f][1, 10]phenanthroline, dmb = 4,4'-dimethyl-2,2'-bipyridine) and [Ru(dmb)_2(DAPIP)](ClO_4)2 (2) (DAPIP = 2-(2,4-diaminophenyl)imidazo[4,5/][1,10]phe-nanthroline), were synthesized and characterized. The DNA-binding behaviors of these complexes have been studied by UV-Vis absorption titration, viscosity measurements, and photocleavage. The DNA-binding constants are 7.39 (±0.16) × 10~4 (5 = 2.68) and 2.73 (±0.16) × 10~4(molL~(-1))~(-1) (s = 0.64) for 1 and 2, respectively. Their evaluation as cytotoxic agents on different cancer cell lines was investigated with IC_(50) values of 59.5, 51.3, and 70.3 μ mol L~(-1) for 1, > 100, 87.9, and 77.9 μ mol L~(-1) for 2 against BEL-7402, HepG-2, and MCF-7 cells, respectively. Complex 1 is more active than 2 against selected cancer cell lines. The apoptosis induced by these complexes was studied. Cellular uptake showed that these complexes could enter into the cytoplasm and accumulate in the nuclei. The cell cycle arrest and antioxidant activity against hydroxyl radicals were also investigated.