Study On Synthesis And Antitumor Activity Of Polypyridine Iridium(Ⅲ)complexes Containing Amino And Nitro Group

Cancer is a common disease that endangers human health.The number of cancer patients has increased year by year.Because of its high recurrence rate and mortality rate,it has become a worldwide problem.The main treatments for cancer include surgical resection,chemotherapy,and radiation therapy.In recent years,more and more patients choose chemotherapy after comprehensive consideration of various factors.At the same time,researchers also pay more attention to the field of chemotherapy.The sciensts are committed to the exploration of high-efficiency and low-toxicity chemotherapy drugs.Nowadays,the development of anti-tumor drugs is diversified.Metal complexes have been favored by many scientists,and many breakthrough achievements have been made,such as cisplatin and oxaliplatin.However,there are still many problems to be solved in the application of these drugs.Therefore,enhancing drug specificity and targeting,reducing toxic side effects and adverse reactions are important aspects in studying such drugs.In this paper,10 metal iridium（III）complexes were synthesized and characterized ESI-MS,UV-Vis,IR,¹H NMR and ¹³C NMR.Evaluation in vitro toxicity found that these complexes against the selected cancer cell lines show a certain toxicity,and the anticancer mechanism was also investigated.In this study,the antitumor activity and mechanism of the drugs were evaluated from the following aspects:Firstly,the toxicity of the complexes in vitro was assayed by MTT colorimetry,and the results indicate that these complexes had a good inhibitory effect on the proliferation of the cancer cell lines.Then,through AO/EB staining method and localization assay,it was found that the complexes could enter into the cells and cause apoptotic morphological changes.The effects of complexes on DNA damage were studied by comet experiment.The results showed that the complexes could induce DNA fragmentation and damage.Qualitative and quantitative analysis of intracellular calcium concentration,mitochondrial membrane potential changes,reactive oxygen species levels,autophagy,cytochrome c and tubulin were carried out under fluorescence microscopy,MD ImageXpress Micro and Flow Cytometry.The results showed that these complexes could enhance intracellular calcium concentration,induce a decrease in the mitochondrial membrane potential,and promote the production of reactive oxygen species and the release of cytochrome c.And it can inhibit tubulin aggregation and block the process of cell mitosis.In addition,most complexes can induce autophagy.Transwell assay suggested that the complex can inhibit cell invasion.Finally,the signal pathway of apoptotic induced by the complexes was explored by western blot,which demonstrated that the complexes could up-regulate the expression of Bax,Bid and Bad proteins and down-regulate the expression of Bcl-2 and Bcl-xL proteins in Bcl-2 family.The release of apoptotic active substances lsuch as cytochrome c in the mitochondria causes a cascade reaction of caspase family proteins,and further induce apoptosis.In conclusion,these iridium（III）complexes can inhibit the growth of tumor cells and induce apoptosis through ROS-mediated mitochondrial apoptotic pathways.