Synthesis Of A Series Of Silver&Copper Complexes With 5-Fluorouracil-1-yl Acetic Acid As The Ligand And Their Anticancer Activity

5-Fluorouracil（5-FU）,as a major anticancer drug in the treatment of solid tumors,has limited its clinical application due to its strong toxic and side effects.It is a hot and difficult point how to reduce the toxic and side effects and improve the anticancer efficacy through chemical modification or targeted release of drug delivery systems in current anticancer research.Aiming at the synergistic effect and targeting effect of anticancer activity,based on sensitivity,low toxicity to human cells,diversified coordination and other characteristics of silver,and based on drug synergy,important cellular components,unique electronic structure and other characteristics of copper,as well as the principle of coordination substitution and drug splicing,in this paper,the carboxyl ligand was introduced into 5-fluorouracil molecule to reduce its toxic and side effects and realize the coordination functionalization of anticancer active drug molecules.The silver/copper anticancer functional complexes were constructed with 5-fluorouracil-1-yl acetic acid（5-FUAA）as the main ligand and tricyclohexylphosphine as the co-ligand.The structures was characterized by X-ray diffraction,infrared,elemental analysis and other methods.In order to explore the interaction mechanism between the target complexs and calf thymus DNA（CT-DNA）,UV-visible absorption spectroscopy was used to record the changes in the height and position of the absorption peaks under different p H values（6.2,7.2,8.2）.Through correlation analysis and literature comparison,it was found that various target complexes had the strongest binding ability with CT-DNA under neutral conditions.Therefore,fluorescence spectroscopy and electrochemical methods were used to further study the interaction between each complex and CT-DNA under neutral conditions.The experimental results of the three methods were consistent,indicating that the five target complexes interact with CT-DNA in an electrostatic mode.In order to explore the anticancer activity of the target complexs,the CCK-8 method was used to detect and calculate the half inhibitory concentration(IC₅₀)of the ligand and anticancer functional complex against MDA-MB-231（human breast cancer cells）and HCT116（human colon cancer cells）under the condition of near-infrared irradiation or not,and the relationship between the structure and the effect was discussed.The results showed that the five complexes had good anticancer activity,and the IC₅₀of the five complexes were in the micromolar range with the IC₅₀of 1-100μM.The IC₅₀of two silver complexes was 4-9μM,which was more effective than that of 5-FUAA.The results of this study showed that the anticancer activity of one of the target complexes was higher than that of 5-FUAA in vitro,and the active center of the original drug and the active center of the metal had a synergistic effect.In addition,the experimental results of infrared laser irradiation on cells showed that its in vitro anticancer activity was stronger than that of unirradiated cells.It can be concluded that light-controlled targeting was obvious.The above results will provide reliable data of direction leading and early application on synergy and targeted controlled release for follow-up design and research of new anticancer drugs of 5-fluorouracil silver/copper complexes.