Studies On The Synthesis, Characterization And Antitumor Activity Of A Series Of Novel Ruthenium(II) Porphyrin Complexes Targeted To G-Quadruplex DNA

Ruthenium (II) complexes was generally considered worldwide that it would be one of the most promising anticancer metallic complexes since platinum anticancer drugs had been used in clinical. G-quadruplex DNA is a good target for telomerase inhibitor. It is helpful to develop new metallic anticancer agents by studying ruthenium (II) complexes acting on G-quadruplex DNA with high antitumor activity.In this thesis, 15 ruthenium (II) complexes were designed and synthesized using porphyrin as ligands. The complexes were characterized by MS, NMR, electronic absorption spectra and fluorescence emission spectra. On the basis of characterization, the recognition mechanism between complexes and nucleic acid was systematic studied by spectroscopy gel electrophoresis method, etc. The structure-activity relationship (SAP) of ruthenium (II) complexes was discussed by the DFT method. Some complexes were preliminarily tested for their inhibitory activity towards human cervical carcinoma HeLa by MTT. The results showed that:1. 15 ruthenium (II) porphyrin complexes were designed and synthesized. It was confirmed that the products were the target compounds through MS, NMR, etc. All the complexes have not been reported in literature.2. The molecular recognition between the target compounds with CT-DNA was studied by electronic absorption spectroscopy, ethidium bromide (EB)-DNA quenching fluorescent spectroscopy. It is found DNA binding properties was influenced by differences of complexes structure. i) The binding constant of 3-pyridyl complexes to CT-DNA is larger than that of the 4-pyridyl. ii) Supported by dmbpy-based ligand, the binding constant of -OCH3- substituted complexes to CT-DNA is larger than that of -CH3- substituted. Supported by phen-based and bpy-based ligand, the binding constant of -CH3-substituted complexes to CT-DNA is larger than that of -OCH3-substituted. iii)The order of interaction between complexes based different ligands and CT-DNA is bpy>dmbpy>phen. 3. The molecular recognition between the target compounds with human cervical carcinoma HeLa was studied by electronic absorption spectroscopy, ethidium bromide (EB)-DNA quenching fluorescent spectroscopy. It was found the binding constant of compounds supported by phen-based ligand to Hela is larger than that to CT-DNA. The result showed ligands having strong hydrophobicity are beneficial to bind to tumor DNA.4. The molecular recognition between the target compounds with Bel-7402 RNA was preliminarily studied by electronic absorption spectroscopy. The result showed complex has selective effect on human cervical carcinoma HeLa.5. Theoretical calculations of 8 complexes have been carried out applying the density functional theory (DFT) method. It showed that the interaction between complexes and DNA was influenced by the energy of frontier molecular orbit.6. The result of inhibitory activity test showed: in the presence of complex 7 and 9, the growth of human cervical carcinoma HeLa was inhibited. The inhibition rate of the light group was higher than that of no light group. Complex 7 and 9 have photo inhibition and apoptosis effect on human cervical carcinoma HeLa.The above studies showed biological macromolecule was selectively recognized by ruthenium (II) porphyrin complexes. The complexes have potential applied prospects in research of anti-tumor drug.