Design,Synthesis And Antitumor Activity Evaluation Of 4,5-Diarylimidazole N-heterocyclic Carbene Metal Complexes

The concealment,metastasis and drug resistance of cancer make it one of the main causes of human death at current stage.Cisplatin and other platin-based drugs have outstanding antitumor activity and play an important role in chemotherapy of cancer,but their serious side effects and drug resistance are also prominent,which limits their further development to some extent.Therefore,to find new metal antitumor drugs with high efficiency,low toxicity and mechanism differ from cisplatin have become the main goal of inorganic chemists.Recently,N-heterocyclic carbene metal complexes have attracted much attention in the field of antitumor drug development due to their unique stability,structural tunability,and low toxicity.Based on the structural diversity of N-heterocyclic carbene,after reasonable structural design,we introduced 4,5-diarylimidazole group to expand the conjugated system of N-heterocyclic carbene ligand for improveing the stability of N-heterocyclic carbene metal complexes.In this thesis,a total of 51 4,5-diarylimidazole N-heterocyclic carbene metal complexes with six different metal centers(gold,copper,ruthenium,rhodium,platinum and palladium)were synthesized and characterized.The stability of some metal complexes was studied,and it was found that the 4,5-diarylimidazole N-heterocyclic carbene metal complexes(Au6,Rhl,Ptl)have good stability in aqueous solution.MTT assay was used to screen the antitumor activity of six classes metal 4,5-diarylimidazole N-heterocyclic carbene complexes in human breast cancer cell(MCF-7),human colon cancer cell(HT-29)and human liver cancer(HepG2)cell lines.It was found that most of 4,5-diarylimidazole N-heterocyclic carbene metal complexes containing gold(I),rhodium(I)or platinum(II)can inhibit the proliferation of MCF-7,HT-29,HepG2 cancer cells,especially the complex Au6,Rhl and Ptl,which have the best antitumor activity in similar metal complexes(in HpG2 cells,IC50 values are 0.50 ?M,1.33 ?M and 0.33 ?M,respectively).Structure-activity relationship studies were performed on the antitumor activity of 4,5-diarylimidazole N-heterocyclic carbene gold(I),rhodium(I)and platinum(II)complexes.And preliminary research on the potential targets of 4,5-diaryimidazole N-heterocyclic carbene gold(I),rhodium(I)and platinum(II)complexes Au6,Rhl,Ptl were also preformed in this thesis.We found that thioredoxin reductase(TrxR)is a potential target of Au6,both TrxR and DNA may be the potential targets of Rhl,while DNA may be a potential target of Ptl.