Synthesis And Photodynamic Activities Of Molecular Target-based Anticarcinogen

Exploring the new/anti-cancer model and designing highly effective and low-toxicity anti-cancer drugs has always been a focus of attention.Singlet oxygen is a highly active oxidant,which can oxidize with DNA,free amino acids,lipids,proteins and other biological macromolecules,causing cell damage and inducing apoptosis.So,1O2 is often used as a cytotoxic agent for cancer treatment.In photodynamic therapy,1O2 is efficiently generated by illuminating of photosensitizers,but there are defects such as lack of oxygen in the tumor environment and insufficient penetration of light in the body;molecule target drugs achieve precise target in cancer therapy,but there is a certain resistance.Therefore,it is of great significance and application prospect to attempt to develop an anti-cancer model that combines the precise and low toxicity of photodynamic therapy and high-efficiency of targeted therapy.So,my job is Committed to designing a new type of efficient molecular targeted antitumor drugs,connecting target molecules(Erlotinib and Gefitinib)with endoperoxide.It can not only realize molecular targeted therapy,but also solve the problems of hypoxia environment and the poor laser penetration in tumor tissue during the PDT to achieve more efficient anti-cancer modes.The main work and results of this article are described below:1)Eight compounds were obtained through organic synthesis,of which six compounds were not introduced in various journals and are new compounds.The structures of the compounds were confirmed by 1H NMR 13C NMR HRMs.2)The ultraviolet-visible absorption spectra and fluorescence emission spectra of Erlotinib-endoperoxide(Y3-1 series compounds)and Gefitinib-endoperoxide(Y5-1 series compounds)were studied.This study explored the release of singlet oxygen from compounds at different temperatures.The results showed that the half-life of the compound was:0-90 min,ti/2=185 min(Y3-1,37?);t1/2=216 min(Y5-1,37?);t1/2=936 min(Y5-1,250C).3)The ability of the compounds of Y3-1 and Y5-1 system to inactivate tumor cells was determined by MTT assay,and 4 different cancer cells were selected.The results showed that in different cancer cells,the target compounds had higher toxicity than the control compounds;The ability of the drugs(Y3-1 and Y5-1)to produce ROS was determined by probe.They can release of singlet oxygen slowly in the dark at 37 ? due to the endo-peroxo bridge,so they all showed higher ability of ROS produced in different cancer cells.The targeting of the compounds were verified by the cell uptake cleavage assay.The results showed that the target compounds retained the targeting activity of the targeting molecules and exhibited better targeting.The confocal laser microscopy images showed that the compounds were well localized in mitochondria and lysosomes.In summary,the compounds of Y3-1 and Y5-1 synthesized in this article have a good targeting to inhibit EGFR and efficiently inactivate tumor cells,and are expected to be developed into a new type of highly effective and low toxicity anticancer drugs.