Synthesis,Characterization And Antitumor Activity Of Triphenylphosphine Ruthenium(Ⅲ) Complexes With Reduced Schiff Base

In the world,cancer is a major disease that causes death.In the late 1960s,the discovery of cisplatin brought hope for the treatment of cancer.However,with the increase of treatment time,cisplatin also showed its shortcomings of large side effects and high drug resistance.Therefore,it is necessary to search for new metal anticancer drugs,among which ruthenium metal complexes are expected to be therapeutic agents with biological activity due to their diverse structures.Schiff bases have attracted much attention for a long time due to their unusual structural properties and biological activities in various applications.Different Schiff base ligands with various uses and variable tooth numbers can be prepared through the aldehyde amine condensation reaction.At the same time,the presence of electron donor atoms in the Schiff base is considered to be a good chelating agent for coordination with metal ions,and its biological activity is enhanced when it is coordinated with metal ions.Therefore,Schiff base complexes are expected to become excellent tumor therapeutic agents,which can be used to treat platinum-resistant tumors or as an alternative to platinum-based chemotherapy.Based on the above viewpoints,15 different reduced Schiff base tetradentate ligands and their corresponding triphenylphosphine ruthenium（Ⅲ）complexes were designed and synthesized,and their structures were characterized.Finally,the in vitro antitumor activity,DNA/BSA binding ability and stability of ruthenium complexes were determined.The results are as follows:（1）Fifteen different reduced Schiff base tetradentate ligands and their corresponding triphenylphosphonium ruthenium（Ⅲ）complexes were designed and synthesized,and characterized by IR,¹H NMR and HRMS.The results show that the new Ru-N and Ru-O bonds are formed by the coordination of ruthenium with N₂O₂in the ligand,which is consistent with the expected results.（2）The antitumor activities of 15 ligands and their complexes against HeLa,A549 and MCF-7 human tumor cell lines in vitro were determined by MTT method,and cisplatin was used as positive control.The results showed that all the complexes exhibited excellent cytotoxicity in vitro（IC50=1.63-31.12μM）to the three human tumor cell lines,and most of them were stronger than cisplatin.Among them,complex C5 has the strongest cytotoxicity,but because it causes a large number of tumor cells to die at a very low concentration,it is not conducive to further study.Therefore,complex C4 was selected and MCF-7 was used as the model to further study its specific mechanism.The results showed that complex C4 could increase the intracellular ROS level in a concentration-dependent manner and induce the late apoptosis of MCF-7 cells.（3）The interaction mode and intensity between the complex and CT-DNA/BSA were determined by UV-Vis,fluorescence spectrum and CD.The results show that the complex binds to CT-DNA in an intercalation mode,and the binding ability of complex C6 is the strongest.Moreover the complex can also bind to BSA,and there is only one binding site,among which complex C4 has the strongest binding ability to BSA.（4）The stability and antioxidant activity of the complex were measured by UV-Vis.The results show that the complex has good stability and antioxidant activity,and its antioxidant capacity is higher than that of standard antioxidant ascorbic acid.