Synthesis And Anticancer Activity Of Disulfide Derivatives Based On Phthalimide

Cancer is always main public health problem threatening human health.The report showed that millions of people worldwide die of cancer every year.At present,most drugs have problems in higher side effect and tolerability,the development of new and effective antitumor drugs has great significance.Phthalimide derivatives have extensive biological activities,antitumor,antiinflammatory,anticonvulsant,antibacterial,antiangiogenesis,immunomodulation,antialzheimer’s disease and antituberculosis,etc.It is reported that disulfide derivatives also have a variety of biological activities such as antitumor and anti-inflammatory.Based on the diversity of biological activities of phthalimide derivatives and disulfide derivatives,relevant people have attracted wide attention.Based on the above biological activity characteristics,20 disulfide derivatives containing phthalimide were synthesized,and the structures of these compounds were characterized by IR,¹H NMR,¹³C NMR and HR-ESI-MS.Using 5-FU（5-fluorouracil）and PX-12（1-methylpropyl-2-imidazolyl disulfide）as positive control drugs,they were tested for their antiproliferative activity against three cancer cells A549（human lung cancer cells）,Hela（human cervical cancer cells）,MCF-7（human breast cancer cells）and normal cells L929（mouse fibroblasts）by CCK-8 assay..Experimental results show that all compounds showed different degrees of antiproliferative activity.For A549 cells,compound 9b has the best antitumor activity with IC50 value of 2.86μmol/L;for Hela cells,compounds 6b and 6c showed excellent antiproliferative activity,with IC₅₀ value of 2.94μmol/L and 3.20μmol/L,respectively;for MCF-7cells,compound 9b showed the highest antitumor activity with IC50 value of 3.21μmol/L;for L929 cells,most compounds showed lower cytotoxicity.In summary,the twenty compounds exhibited various degrees of antitumor activity against the three types of cancer cells,and most of the compounds exhibited lower cytotoxicity to normal cells.The above results have laid a good foundation for the study of structure-activity relationship and mechanism of action.