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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, 1H NMR and 13C 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.

A new ligand THPDP (THPDP = 11-(6,7,8,9-tetrahydrophenazin-2-yl)dipyrido[3,2-a:2′,3′-c]phenazine) and its iridium(III) complex [Ir(ppy)2(THPDP)]PF6 (Ir-1) was synthesized and characterized by elemental analysis, IR, ESI-MS, 1H NMR and 13C NMR. The cytotoxicity in vitro of the complex against cancer cells B16, A549, Eca-109, SGC-7901, BEL-7402 and normal NIH 3T3 cell lines was evaluated using MTT method. The IC50 values of the complex toward B16, A549 and Eca-109 cells are 1.0 ± 0.02, 1.4 ± 0.03 and 1.6 ± 0.06 μM, respectively. The apoptosis was investigated with AO/EB and DAPI staining methods. The complex shows strong ability to inhibit the cell growth in B16, A549 and Eca-109 cells. Ir-1 can induce apoptosis, increase the intracellular ROS level, and cause a decrease in the mitochondrial membrane potential. The intracellular Ca2+ level and the release of cytochrome c were studied under a fluorescent microscope. The cell invasion and autophagy were also performed, and the cell cycle arrest was assayed by flow cytometry. The expression of Bcl-2 family proteins, PI3K, AKT, mTOR, P-mTOR was investigated by western blot. The results show that the complex induces apoptosis through ROS-mediated mitochondria dysfunction and inhibition of AKT/mTOR pathways. These findings are helpful for design and synthesis of iridium(III) complexes as potent anticancer drugs.

A new ligand MHPIP (MHPIP = 2-(1-methyl-1 H -pyrazol-4-yl)-1 H -imidazo[4,5- f ][1,10]phenanthroline) and its three ruthenium (II) complexes [Ru(N-N) 2 (MHPIP)](ClO 4 ) 2 (N-N = phen: 1,10-phenanthroline 1 ; dmp = 2,9-dimethyl-1,10-phenanthroline 2 ; ttbpy = 4,4′-ditertiarybutyl-2,2′-bipyridine 3 ) were synthesized and characterized. The cytotoxic activity in vitro was studied by MTT method. The complexes 1 – 3 show moderate cytotoxic effects on the cell growth in HepG2 cells with an IC 50 value of 25.5 ± 3.5, 35.6 ± 1.9 and 27.4 ± 2.3 μM, respectively. The apoptosis was investigated with AO/EB and Annex V/PI staining methods and comet assay. The reactive oxygen species, mitochondrial membrane potential were investigated under a fluorescent microscope. Autophagy assay shows that the complexes can cause autophagy and up-regulate the expression of Beclin-1 protein. Additionally, the complexes inhibit the cell growth in HepG2 cells at G0/G1 phase, and the complexes can regulate the expression of caspase 3 and Bcl-2 family proteins. The studies demonstrate that the complexes induce apoptosis in HepG2 cells through DNA damage and ROS-mediated mitochondrial dysfunction pathways.