Synthesis And Anticancer Activity Of Disulfide Derivatives Based On N-Phenyl-1,8-Naphthalimide

With the gradual increase in the number of cancer diagnoses in recent years,cancer has become a major disease hindering the increase in life expectancy in the world.Therefore,the development of highly effective and selective anticancer drugs is still a top priority.Disulfide derivatives have various biological activities such as antitumor,antibacterial,and antiviral.According to reports,as an excellent DNA intercalator,1,8-naphthalimide compounds also have a variety of biological activities,such as antibacterial,antifungal,antiviral,antiherpes,antiinflammatory,antitrypanosomiasis,and antitumor activities,etc.Therefore,it has caused widespread concern.Based on the above mentioned biological activity characteristics,21 unreported1,8-naphthalimide disulfide derivatives were designed and synthesized in this thesis,and characterized their structures by IR,¹H NMR,¹³C NMR and HR-ESI-MS.5-FU（5-fluorouracil）and PX-12（1-methylpropyl-2-imidazole disulfide）were used as positive control drugs,all compounds have been tested for antitumor activities against three kinds of cancer cells human breast cancer cells MCF-7,human liver cancer cells SMMC-7721 and human cervical cancer cells He La,and cytotoxicity against a kind of normal cells mouse fibroblast L929 by CCK-8 method.The test results showed that compounds 7d and 8a had the remarkable antiproliferative activity against MCF-7 cells,and their IC₅₀ values were 3.19 and3.83μmol/L,which were better than the two positive control drugs 5-FU and PX-12;compounds 7c,7d,8a and 8b had high efficient antiproliferative activity against SMMC-7721 cells,and their IC₅₀ values were 3.60,3.75,1.84 and 3.55μmol/L,which were better than the two positive control drugs;compound 6c had the best antiproliferative activity against He La cells,and its IC₅₀ value was 2.14μmol/L,which was better than the two positive control drugs.For L929 cells,most of the compounds showed lower cytotoxicity than the two positive control drugs.In summary,the 21 compounds synthesized in this article exhibited different degrees of proliferation inhibition on three cancer cells,the activities of some compounds were better than the two positive control drugs,and most of the compounds showed low toxicity to normal cells L929.The above results laid the foundation for the study of its structure-activity relationship and mechanism of action.