Synthesis And Antitumor Activity Of Acetylene Gold(I) Complexes

As effective anticancer chemotherapy drugs,metallic drugs represented by platinum drugs have been widely used in the treatment of various types of cancer.However,side effects such as drug resistance caused by the anticancer treatment of platinum drugs has made people start to explore other transition metal drugs.Auranofin has a good anticancer activity,and the stability of the gold?I? complex,lipophilic-hydrophilic and redox properties can be adjusted by changing the ligand to obtaina better anticancer active gold complex.Common gold?I? complex ligands include organophosphorus,mercaptans,N-heterocyclic carbene?NHC? and alkynes.The acetylene gold?I? complexes have attracted increasing attention because of the convenient synthesis,stable structure,and good anti-cancer activity.34 new acetylene gold?I? complexes of series A,series B and series C were designed and synthesized,and their structures were characterized by NMR.The A series of organophosphorus ligand was diphenylpyridylphosphine ligands,the B series of organophosphine ligand was tricyclohexylphosphine ligand,and the C series of organophosphorus ligand was triphenylphosphine and substituted triphenylphosphine ligand.The anti-proliferative activity of these newly synthesized acetylene gold?I? complexes was determined via MTT colorimetric assay,including A549?human lung cancer cell line?,HT29?human colon cancer cell line?,and hepg-2?human liver cancer cell line?.The results showed that the structure of the acetylene gold?I? complex had a correlation with the anti-tumor activity:?1?The IC₅₀ values can be obtained after screening A series including diphenylpyridylphosphine ligands and the C series including triphenylphosphine and substituted triphenylphosphine ligand,which were similar to or even lower than the positive control,and the IC₅₀ value in the B series including tricyclohexylphosphine ligand was higher than the positive control.These results indicate that the organophosphine ligands of the acetylene fund complexes are aromatic hydrocarbons and better than aliphatic hydrocarbons.?2?When the alkyne ligand is partially substituted by an amino group,the gold complex exhibits positive anticancer activity.These results provide a reference for the synthesis of antitumor drugs in the future.In addition,since acetylene gold?I? complex PyPh₂P-Au-C?CCMe₂Cl?A11? was significantly better in anti-tumor activity compared to the positive control drug,it was detected in the viewpoint of cell cycle,apoptosis,reactive oxygen and mitochondrial membrane potential changes.After 24 hours'co-treatment of the compound A11 acetylene gold?I? complex?20?M? and the positive control drug?150?M?,we found cell cycle manifests as G1/S phase transmission block and acetylene gold?I? complex can induce apoptosis,increase active oxygen concentration,and decrease mitochondrial membrane potential.Therefore,we consider the mitochondrial pathway may play a important role in mediating the induction of apoptosis by compound A11.