Synthesis And Antitumor Activity Of Benzisoselenazolone Derivatives Containing 1,2,4-triazole

Selenium plays a vital role in human physiological activity.Ebselen contains benzisoselenazolone that can simulate the effect of GSH-Px and has showed many kinds of biological activity,such as anti-oxidation,anti-tumor and so on,which is recognized as one of the most potential drugs.1,2,4-triazole derivatives have a small side effect,high biological activity and drug targeting,etc.“S–C” key is biocompatible and help to show higher biological activity.As a basis,Ebselen was used as the lead compound,14 substituted sulfur-1,2,4-triazole derivatives based on benzisoselenazolone were designed and synthesized.The structure of all the target compounds were confirmed by IR,1H NMR,13 C NMR and HR-ESI-MS.In order to find out the organoselenium compound with high antitumor activity,these target compounds were evaluated for their cytotoxicity in vitro against human cancer cell A549,SMMC-7721,Hela and L929 by CCK-8 assay.The majority of them displayed lower antitumor activities than ethaselen.But,ethyl and n-propyl substituted derivatives 9b and 9c,displayed highly effective biological activities with IC50 values of 6.02 and 6.01 ?M,respectively,and the activity was superior to ethaselen.In addition,a similar effect was observed for compound 9n possessing 4-nitro substituent at the phenyl ring,with IC50 value of 8.91 ?M.Apparently,in SMMC-7721 cells,short chain substituted derivatives,including 9a,9b and 9c relatively exhibited better activities than long chain substituted derivatives,including 9d,9e,9f and 9g.In Hela cells,most of the tested compounds showed weaker antiproliferative activities than positive controls ethaselen and 5-fluorouracil.But,compounds 9k and 9n,displayed much better potency than ethaselen and 5-fluorouracil.Especially noteworthy is compound 9n,showed significant antiproliferative activities with IC50 value of 3.94 ?M.In A549 cells,most of the compounds exhibited antiproliferation with different degrees,and compound 9n,exhibited the best inhibitory effect with IC50 value of 9.14 ?M.But all compounds showed lower antiproliferative effects than positive controls ethaselen and 5-fluorouracil.In L929 cells,most of the compounds exhibited weak cytotoxic activity,and all compounds showed highly lower cytotoxic effect than 5-fluorouracil.Especially compound 9h,9i,9l,9m,showed low cytotoxic effect with IC50 value of greater than 50 ?M.In summary,the introduction of differetent groups had a signifiiciant impact to biological activity of compounds and it laid a foundation for further research of the kind of derivatives.