Four novel oxidovanadium(IV) complexes, [VO(hntdtsc)(PHIP)] (1) (hntdtsc = 2-hydroxy-1-naphthaldehyde thiosemicarbazone, PHIP= 2-phenyl-imidazo[4,5-f]1,10-phenanthroline), [VO(hntdtsc)(DPPZ)](2)(DPPZ= dipyrido[3,2-a:2',3'-c]phenazine), [VO(satsc)(PHIP)](3) (satsc=salicylaldehyde thiosemicarbazone), and [VO(satsc)(DPPZ)](4), have been prepared and characterized. The chemical nuclease activities and photocleavage reactions of the complexes were tested. All four complexes can efficiently cleave pBR322 DNA, and complex 1 has the best cleaving ability. The antitumor properties of these complexes were examined with three different tumor cell lines using MTT assay. Their antitumor mechanism has been analyzed using cell cycle analysis, fluorescence microscopy of apoptosis, and Annexin V-FITC/PI assay. The results showed that the growth of human neuroblastoma (SH-SY5Y, SK-N-SH) and human breast adenocarcinoma (MCF-7) cells were inhibited significantly with very low IC50 values. Complex 1 was found to be the most potent antitumor agent among the four complexes. It can cause G0/G1 phase arrest of the cell cycle and exhibited significant induced apoptosis in SK-N-SH cells and displayed typical morphological apoptotic characteristics. In addition, they all displayed reasonable abilities to scavenge hydroxyl radical, and complex 1 was the best inhibitor.
Three mononuclear oxovanadium complexes [VO(Hbid)(CF3PIP)] (1) (Hbid=(E)-2-(2-hydroxybenzylideneamino)isoindoline-1,3-dione, CF3PIP=2-(2-trifluoromethyl phenyl)imidazole[4,5-f][1,10] phenanthroline), [VO(Hbid)(m-CF3PIP)]; (2) (m-CF3PIP=2-(3-trifluoromethyl phenyl)imidazole [4, 5-f][1,10]phenanthroline) and [VO(Hbid)(p-CF3PIP)]; (3) (p-CF3PIP=2-(4-trifluoromethyl phenyl) imidazole[4,5-f][1,10]phenanthroline) have been synthesized and characterized by elemental analysis, IR, molar conductance, ES-MS and 1 H NMR. The DNA-binding properties of these complexes were studied by using UV-Vis absorption titration, fluorescence spectra, viscosity measurements and thermal denaturation studies. The results show that 1, 2 and 3 interact with calf thymus DNA (CT-DNA) by intercalation modes and the magnitude of their intrinsic binding constants (Kb values) follows the order: 2 < 1 < 3. Furthermore, their photocleavage properties with pBR322 plasmid DNA were investigated by agarose gel electrophoresis experiments. The DNA cleavage capacity of complex 3 is also stronger than that of 1 and 2.
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