Synthesis And Anti-cancer Activity Of Gold(Ⅰ) Complexes

Gold complexes are a class of compounds which were synthesized by Au（Ⅰ）or Au（Ⅲ）ions with ligands that contain nitrogen,phosphorus,sulfur or carbon etc.The geometrical configuration of the gold complex is variable,and it exhibits two,three or four coordination in most cases.Gold complexes also have special electronic structure and variable redox state,which exhibit excellent catalytic properties,rich optical properties and special biological activities,and they have very broad application prospects in the catalysts,optical materials,protein inhibitors and anti-cancer drugs.In particular,it revealed a new aspect in the field of anti-cancer drugs for gold complexes after the discovery of the anti-cancer activity of Auranofin.People have been successively synthesized a number of gold complexes by modifying and improving ligands,and those gold（Ⅰ）or gold（Ⅲ）complexes have good anticancer activities.The structure of gold complexes is closely related to anti-cancer activities.When the gold complex enters the organism,it can occur ligand exchange reaction with serum albumin,thioredoxin reductase,glutathione peroxidase and other substances,then it form a protein-gold ion complex and exert anti-cancer activities.Therefore,the stability of the chemical bond of gold complex can directly affect the anti-cancer activities.Compared with porphyrin gold complexes and some nitrogen-containing heterocyclic carbene gold complexes,alkyne-like gold complexes and sulfur-containing gold complexes have moderate chemical bond stability,and more prone to occur ligand exchange reaction with the protein of cancer cells,which greatly increases its possibility as a target for anti-cancer drug development.Therefore,this paper selects the alkyne and containing sulfonium compounds as ligands,and synthesis of new gold complexes,in order to obtain lead compounds which have good anti-cancer activities.In this thesis,two series of gold complexes containing alkyne groups or sulfur-containing groups were designed.At present,37 new gold complexes were synthesized and characterized.Among them,there are 31 alkynes series gold complexes including 5 crystals and 6 sulfur-containing gold complexes including 2 crystals.Simultaneously,that were used the ¹H-NMR,³¹P-NMR and X-ray single crystal diffraction to characterize those gold complexes.In addition,we selected A549,HepG2,Ht29 cancer cell lines to screen the anti-cancer activities of the partial gold complexes.The results revealed that multiple compounds had good anti-cancer activities.For A549 lung cancer cells,the anti-cancer activities of compound A8,B8,B9,B10 was similar to that of Auranofin,the IC-₅₀ of compound A8 was 3.77μM;For HepG2 liver cancer cells,the anti-cancer activities of compound A1,A8,B1,B3,B4,B7,B8,B9,B10 was similar to that of Auranofin,the IC₅₀ of compound B4 was 4.363μM;For Ht29 colon cancer cells,the anti-cancer activities of compounds A1,A8,B1,B4,B7,B8,B9,B10 was similar to that of Auranofin,and the IC₅₀ of the compound B1 was 6.25 μM.To sum up,a part of new compounds have good anti-cancer activities which can provide the judgment basis for the later experiment.