Studies On The Anticancer Activity And Mechanism Of Phenanthroline Derivatives And Ruthenium(ⅱ) Complexes

Both in developed and developing countries, the high death rate of cancer hazards to human health made it become one of the most serious diseases. Chemotherapy is an important mean for cancer treatment, but it has side effects. And it's the goal for researchers to seek for effective, low toxic anti-cancer drug. Metal complexes, especially phenyl-ruthenium complex attracted extensive attention since the finding of cisplatin. Compared to cisplatin, phenyl-ruthenium complex has the advantages of low toxicity. In this paper, a series of phenanthroline derivatives and phenyl-ruthenium(II) complexes coordinated by phenanthroline derivatives were synthesized. Specific works as follows:1. Research progress of ruthenium complex, anti-tumor mechanism were introduced. And the significance of molecular recognition between ruthenium complexes and DNA also was clarified. Based on this study, the research purpose and basis of this paper were described .2. A series of phenanthroline derivatives containing multi coordination sites were synthesized with different substituted alkyl group and the location. The relationship between ruthenium complex and the anti-tumor activity was studied by structure-activity relationships.3. Phenanthroline derivatives of the anti-tumor activity were investigated by MTT assay. Studied on A549 cell apoptosis induced by p-BrPIP by FCM and mechanism by western blot and RT-PCR. Four single crystal phenanthroline derivatives were obained by solvent evaporation method. The results show that the activity order of the same substituent compounds is ortho->meta->para-. The activity of large compounds is weaker than the small steric. The PCR and western blot show that p-BrPIP reduces the activity of NF-κB to inhibit A549 cell proliferation by lower the C-myc expression.4. The different phenyl-ruthenium(II) complexes with [(η⁶-C₆H₆)RuCl(L)]⁺ in the general formula (L= Phenanthroline derivatives) were synthesized and characterized by ESI-MS and NMR.5. The anti-tumor activity of phenyl-ruthenium(II) complexes on A549, SMMC7721, and SW620 was investigated by MTT assay. A549 cell apoptosis induced by p-BrPIP was reseached by flow cytometry. The results show that benzene ruthenium complexes have much higher inhibition towards A549 than the other tumor cells, but have little inhibition towards SMMC7721 and SW620. The phenomenon explained that ruthenium(II) complexes have selective inhibition towards tumor cells. A549 cell apoptosis was induced by ruthenium(II) complexes 9 and 13.