DNA-binding, molecular docking studies and biological activity studies of ruthenium(II) polypyridyl complexes

Anticancer properties of chemically synthesized compounds have been evaluated for efficacy and selectivity. A new ligand PTCP (PTCP = 2-phenanthren-9-yl-1H-1,3,7,8-tetraazacyclopenta[l] phenanthrene) and its three new ruthenium(II) polypyridyl complexes [Ru(N-N)(2)(PTCP)](ClO4)(2) (N-N: phen = 1,10-phenanthroline 1; dmp = 2,9-dimethyl-1,10-phenanthroline 2; ttbpy = 4,4 '-di-tert-butyl-2,2 '- bipyridine 3) were synthesized and characterized by elemental analysis, ESI-MS, IR, H-1 NMR and C-13 NMR. In this report, we investigated the cytotoxicity in vitro of the complexes against several cancer cell lines SGC-7901, HepG2, HeLa, SiHa and normal cell NIH3T3. The results show that complexes show highly anti-proliferation activity toward SGC-7901 and low cytotoxic activity against normal cell NIH3T3. The relationship between anti-proliferation and molecular interaction mechanism of the complexes was also elucidated. The apoptosis was assayed by flow cytometry. The changes of mitochondrial membrane potential and the ROS levels were measured by flow cytometry. The cell invasion, cell cycle arrest and the expression of Bcl-2 family proteins were studied in detail. N-Acetylcysteine (NAC) was used in several experiments to testify the effect of the complexes on apoptosis. The results demonstrate that the complexes induce apoptosis in SGC-7901 cells through a ROS-mediated mitochondrial dysfunction pathway, which was accompanied by the regulation of Bcl-2 family proteins. In addition, the interaction of the complexes with calf thymus DNA (CT-DNA) shows that the complexes interact with DNA through partial intercalation mode.