The Anti-tumor Activities Researches By Seriels Of Multi-nitrogen Compounds

Apoptosis means the procedural death of cells. The research of antitumor drugs inducing apoptosis has become the main orientation of antitumor drugs analysis. This thesis gives a brief introduction of the theoretical basis of antitumor drugs targeting DNA and some DNA cleavage reagents used in clinic. In addition, a brief review of the research development of macrocyclic polyamine compounds and photosensitizer compounds in the recent years is also given. Furthermore, it summarizes the cell cycle and apoptosis related with cell proliferation and death, which accounts for the relationship between apoptosis and antitumor drugs. Finally, multiple research methods of apoptosis analysis are put forward and epitomized.In this research, DNA hydrolysis cleavage regents and DNA photosensitizer were chose respectively, for the purpose of revealing their relationship with their activity of inducing tumor cell apoptosis. The DNA cleavage reagents used in this research is1,7-dimethyl-1,4,7,10-tetraazacyclododecane (DMC), as a respect of non-metallic macrocyclic polyamine compounds. While, DNA photosensitizers are divided into two classes, one is pyrene polyamine compounds, which exists as a dual-model combined DNA minor groove with insert pattern, the other one is cationic ester porphyrin. A preliminary study about the antitumor activity of macrocyclic polyamine, pyrene and porphyrin compounds is also carried out.(1) In this thesis, we synthetized compound DMC firstly, and then analysed the cleavage activity of DMC and its different metal complexes by gel electrophoresis imaging technology, which indicates that the strongest cleavage activity is presented by DMC and Co(Ⅱ)-DMC complex. MTT shows both DMC and Co(Ⅱ)-DMC complex own a better hydrolysis cleavage activity to Hela and A549cell lines. While, the analysis detected by cytomorphology, DNA gradient gel electrophoresis and PI staining shows that DMC possesses the ability of inducing Hela apoptosis but shows no activity for A549cell lines.(2) A series of pyrene polyamide compounds synthetized in our lab is chose for the deep study, which presents an excellent activity of photocleaving UNA and strong phototoxicity to Hela, A549and MCF-7cell lines. What’s more, the ability of inducing tumor cell apoptosis of these compounds is also verified by lots of methods including Annexin V-FITC/PI double staining.(3) Three cationic erster porphyrin derivates with different substituents that synthetized in our lab were chose in this study. We found that under the excitation of visible light, they all exhibit a good ability of inducing cell apoptosis and good tumor cytotoxicity. While, they are all harmfulless if there is no illumination. Experiments revealed that the lethality to Hela cell of these three porphyrin in much stronger than Photofrin that used in clinic, which indicates that these compounds can be lucubrated as potential photodynamic regents.In allusion to the study of these three types of multiple nitrogen DNA cleavage regents, we can conclude that the antitumor activity of these DNA cleavage regents is related with DNA cleavage ability, as well as the ability of inducing cell apoptosis. Furthermore, it is confirmed that the cytotoxicity of drugs is not realized by inducing cell apoptosis, but is concerned with the tumor cell lines we chose.