Synthesis And Antitumor Activity Of Disulfide Derivatives Based On 2-phenyl-3-substituted Phenyl-1,2,4-triazole

1,2,4-triazole and their derivatives are found to be possessed a wide array of pharmacological properties,such as antitumor,anticonvulsant,antibacterial,anti-inflammatory,analgesic,antitubercular,antimalarial,antidepressant,hypoglycemic and thymidine phosphorylase inhibitory properties.Furthermore,disulfide derivatives play a crucial role due to their medicinal properties particularly in targeting tumors.In order to obtain more effective antitumor agent,24 novel disulfide derivatives of 2-phenyl-3-substituted phenyl-1,2,4-triazole were designed and synthesized in this paper,and the structures of the synthesized compounds 7a-7h,8a-8h and 9a-9h were confirmed by IR,¹³C NMR,¹H NMR and HR-ESI-MS.Cytotoxicity of the target compounds to SMMC-7721,Hela,A549 cancer cell lines and L929 normal cell lines was tested in vitro by CCK-8 method using 5-fluorouracil（5-FU）and 1-methylpropyl2-imidazolyl disulfide（PX-12）as positive control drugs.The test results showed that all compounds displayed different degrees of antiproliferation activity against different cancer cells.In SMMC-7721 cells,compound 8g revealed the best inhibitory effect with IC₅₀values of 2.92μmol/L,and its activity was better than 5-FU and PX-12.In Hela cells,compounds 7a,8g,9g and 9h exerted highly effective antitumor activities with IC₅₀values of 6.31,4.31,6.31,and 3.97μmol/L,respectively,and their activities were better than 5-FU and PX-12.In A549 cells,compounds 7c,9a and 9h revealed significant antiproliferative activity with IC₅₀values of 4.75,4.92,and 3.73μmol/L,respectively,and their activities were better than 5-FU and PX-12.In addition,all compounds showed lower cytotoxicity to normal cell line L929 compared to 5-FU and PX-12.From the above experimental results,it can be seen that the final products synthesized in this paper showed antiproliferative activity against different cancer cells,and most of the synthesized compounds exerted low cytotoxicity against normal cells L929 compared with cancer cells.The above findings lay the foundation for further research on the antitumor activity of such compounds.