Synthesis Of Small Molecule Polypyridine Iridium(?) Metal Complex And Its Antitumor Activity

As we all know,cancer has always occupied the first place in diseases that endanger human health.In the World Health Organization report,more than 10 million humans will lose their lives because cancer cannot be cured.Not only that,this number is still increasing year by year.Increasingly,WHO studies have estimated that cancer patients will increase to 20 million within ten years.So far,humans mainly rely on chemotherapy for treatment.However,the specificity of the chemotherapeutic drugs we currently use is poor.Therefore,"comprehensive chemotherapy" is often used in chemotherapy,that is,the use of two or more chemical drugs at the same time,and large Chemotherapy is used in most patients.Common chemotherapeutics are mainly platinum metal complexes,such as cisplatin,oxaliplatin,and loplatin.Although platinum drugs have played a huge role in the treatment of tumors,the obvious toxic side effects of platinum have limited their use in Clinical promotion and application.Therefore,the search for more effective drugs with less toxic and side effects has become the main direction of research in the field of antitumor drugs.As everyone knows,ruthenium(?),iridium(?)and platinum are transition metals of the same main group.Therefore,based on this principle,three series of small molecule iridium(?)metal complexes have been designed and synthesized in this paper.The structural molecules were characterized by mass spectrometry and nuclear magnetic resonance.In addition,we also conducted antitumor activity studies on three series of iridium(?)metal complexes in terms of cells and biochemistry.The research is mainly divided into two aspects:in vivo and in vitro.In vitro experiments we performed MTT to detect the cytotoxicity of the complexes on various tumor cell lines.The results show that the three series of complexes show high cytotoxicity toward the same cancer cell line.Then,we found that the complex can enter the cell to break down the subcellular organelles and cause apoptosis by AO(acridine orange)/EB(ethidium bromide)staining,Therefore,we further analyzed the complexes inducing apoptotic degree by flow cytometry.Degree of apoptosis caused by substances.Secondly,we further analyzed by high-content cell imager and flow cytometry,and the results showed that most of the compounds synthesized in this paper can induce tumor cell apoptosis through mitochondrial pathway.In addition,cycle detection and western blot experiments were performed.After analysis,the complexes can cause cell cycle arrest and regulate protein expression,which can cause tumor cell apoptosis.We also found that the complex can effectively inhibit tumor cell proliferation through colony inhibition testing.Finally,we performed in vivo activity experiments on the complexes.We first performed acute toxicity experiments to determine the final dose concentration and established a human tumor transplantation model with nude mice,then randomly grouped,observed and measured tumor growth,and finally passed tissues.Sections were used to observe the effects of the complex on the brain,heart,lung,liver,and kidney tissue morphology.The experimental results show that the complex can indeed slow down tumor growth and proliferation,and that the complex has a small effect on various tissues.Finally,it is concluded that the small molecule metal iridium(?)complex designed in this paper has good antitumor activity in vitro and in vivo.