Design And Synthesis Of Chlorin E6-ferrocene Conjugates

Ce6 has achieved good results in both photodynamic therapy?PDT?and sonodynamic therapy?SDT?.Three main elements are required in photodynamic therapy:photosensitizer,light and oxygen.The photosensitizer passes through the ground state?S₀?,the singlet excited state?S₁?and the triplet excited state?T₁?under light irradiation,and then transmits the light energy to oxygen or the stroma.Then oxygen and stroma form reactive oxygen species?ROS?,and thus has the ability to inhibit or kill cancer cells.The development of efficient and low-toxic photosensitizer molecules is one of the important research directions.Ferroptosis is a new cell death method.First proposed by Dr.Brent R.Stockwell's laboratory in 2012,which is different from apoptosis,necrotizing apoptosis and autophagic cell death.The trigger for Ferroptosis is also due to the generation of ROS in the body.Therefore,this subject uses Ce6 as the parent structure,and introduces iron ion donors at positions 17,15,and 13 of the structure.Through the common or synergistic effect of PDT and Ferroptosis,the compound's cytotoxicity to cancer cells can be improved,so that the drug has better efficacy in the treatment of cancer diseases.In this project,nine target small molecules were synthesized,and tested the physical and chemical properties of small molecules such as NMR,UV-Vis,IR,HRMS,etc.In the evaluation of antitumor activity in vitro,Hela cervical cancer cells were selected as the cell lines to be tested.The dark toxicity IC₅₀ values of the target compounds measured by MTT method and the comparison of the parent compounds showed no significant changes;the IC₅₀ values of phototoxicity have decreased to varying degrees,the target compound with the lowest IC₅₀ value is 22 to 23times smaller than that of the parent compound.In the later stage,the process of Ferroptosis caused by the target compound needs to be confirmed and evaluated.The research of this subject is expected to provide a new idea for the design of photosensitizer.