Synthesis Of Carbon-oxygen Coordinated Metal Iridium(?) Nitrogen Heterocyclic Carbene Complex And Its Anticancer Activity In Vitro

Regardless of the level of human development in every region of the world,the high incidence and high mortality of cancer have caused widespread concern in humans.As the number of cancer patients increases,the anticancer drug market has also developed.In recent years,anticancer drugs have been the core area of drug research and development,and their number has shown an increasing trend.Platinum anticancer drugs are currently the most widely used drugs for the treatment of cancer,and their mechanism of action is mainly to block DNA replication,thereby inhibiting the division of cancer cells.However,platinum anticancer drugs also have some problems,such as toxic side effects and drug resistance.Therefore,many research groups at home and abroad have done a lot of work on the research and development of anticancer drugs,expanding the scope of research to non-platinum metal complexes,in order to obtain the complexes of the better anticancer efficacy,lower toxicity,and overcome platinum resistance.In recent years,the anticancer activity of metal iridium???complexes have been reported,and have the potential to become anticancer drugs.In this paper,a series of carbon-oxygen coordinated metal iridium???N-heterocyclic carbene complexes were synthesized and their in vitro cytotoxicity experiments were carried out to further explore the mechanism of action.The main research contents of this paper are as follows:1.Eight phenol oxygen-nitrogen heterocyclic carbene ligands and twelve metal iridium???complexes were designed and synthesized,and characterized by ¹H NMR,¹³C NMR,MS and elemental analysis.The complexes 1-12 exhibited significant in vitro antitumor activity against A549 cells and HeLa cells,and the structure of the iridium???complexes had a significant effect on the activity.The tested complexes were hydrolyzed in aqueous solution and had good solubility.The iridium???complexes showed no binding to 9-methyl adenine and 9-ethyl guanine and no cleavage of plasmid DNA.Therefore,DNA may not be the primary target of these complexes.The complexes captured hydrogen to convert NADH to NAD⁺,producing reactive oxygen species.Increased levels of reactive oxygen species caused a decrease in mitochondrial membrane potential,increased lysosomal membrane permeability,lysosomal damage,and ultimately apoptosis.2.The carboxy-nitrogen heterocyclic carbene ligands and four metal iridium???complexes were designed and synthesized,and characterized by ¹H NMR,¹³C NMR,MS and elemental analysis.In the anticancer activity test of metal iridium???N-heterocyclic carbene complexes 13-16 to A549 cells,complexes 13 and 14 showed very low cytotoxicity?>100?M?,and the anticancer activity of complexes 15 and 16 performed well.The iridium???complex 16was combined with ct-DNA and BSA to initially explore the mechanism of action of the complex in cells.