Synthesis And Antitumor Activity Of Substituted Dibenzo[a,kl] Xanthene Derivatives

Studies have shown that dibenzo[a,kl]xanthene derivatives have good anti-tumor activity,making it a very promising prospect in the field of anti-tumor drugs.However,these compounds have problems such as poor water solubility,high toxicity and side effects.Therefore,the purpose of this thesis is to modify the parent structure of the compound dibenzo[a,kl]xanthene to improve the water solubility and toxicity of the compound,and to study its anti-tumor activity,so as to provide basic research for the subsequent development of such compounds..The specific research content and results of this paper are as follows:1.Synthesis research:a total of 36 new compounds were synthesized（1）At room temperature,methanol or ethanol is the solvent and H₂O₂ is the oxidizing agent to prepare 12 new structure dibenzo[a,kl]xanthene epoxides,where the substituent group is-CONH（CH₂）₂OH epoxy.The yield of compounds is as high as 95%.（2）At a temperature of 40℃,methanol or ethanol is the solvent,FeCl₃ is the catalyst to prepare 20 new configurations ofβ-alkoxy alcohol-dibenzo[a,kl]xanthene.This method has not been reported in the literature.（3）Four identical perixanthene and xanthene derivatives were prepared under two conditions of high temperature and microwave radiation.The yield of microwave method can reach 78%,and the reaction time is only 36 minutes.Based on the previous research of the research group,a compound with a larger conjugate system was prepared to make it better for anti-tumor applications.2.Research on anti-tumor activity:（1）In vitro tumor cell proliferation inhibitory activity test data shows:all the tested derivatives have proliferation inhibitory effect on the tested tumor cells.Specifically,the IC50values of 14a² and 13a² against SGC7901（human gastric cancer cell line）are 5.3±0.2μmol/L and 25.4±1.5μmol/L,respectively.According to the data analysis,the compound with the ethoxy group as the substituent at the position of compound 13c has an excellent inhibitory effect on gastric cancer For compounds whose substituent is methoxy;other data show that:in the derivatives synthesized in this thesis,the compound whose substituent is-COOCH₃has relatively strong cytotoxicity.（2）Experimental studies on the binding of the compound to CT-DNA show that the compound interacts with CT-DNA through insertion,which is the same as the action of anticancer drugs with DNA.（3）The experimental results of the fat-water partition coefficient show that the fat-water partition coefficients are all around 1,and follow the principle that the lipid-water partition coefficient of drug design is less than 5.The smaller the partition coefficient,the better the water solubility.The water solubility of the previous compounds in the research group is Above 2,it can be seen that the water solubility has been significantly improved to achieve the purpose of structural modification of the derivative.