Synthesis, characterization, photocleavage, cytotoxicity in vitro, apoptosis, and cell cycle arrest of ruthenium(II) complexes

Two new ruthenium(II) complexes, [Ru(dmp)(2)(BHIP)](2+) (1) and [Ru(dmb)(2)(BHIP)](2+) (2), were synthesized and characterized by elemental analysis, ESI-MS, and H-1 NMR. DNA-binding constants of these complexes with calf-thymus DNA (ct-DNA) were determined to be 2.09 (+/- 0.18) x 10(4) (mol L-1)(-1) (s = 2.58) and 1.48 (+/- 0.17) x 10(5) (mol L-1)(-1) (s = 1.57), respectively. Viscosity measurements show that 1 and 2 interact with ct-DNA by intercalation. Upon irradiation at 365 nm, 1 and 2 induce cleavage of pBR322 DNA. The cytotoxicity of these complexes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The apoptosis induced by the complexes was studied by flow cytometry. The results of the cell cycle arrest show that 2 can inhibit the proliferation of BEL-7402 cells in the G0/G1 phase.