Synthesis And Antitumor Activity Of Disulfide Derivatives Based On 1,2,4-Triazole

In recent years,through the study of the disulfide compounds people found that it shows various good biological activity,such as antibacterial,antifungal,antitumor activity,anti-hiv activity,etc.,which has attracted widespread attention.Current studies suggest that the mechanism of this compounds of antitumor activity is associated with the thioredoxin/thioredoxin reductase system.1,2,4-triazoles have widely potential application values for its antibacterial,antihypertensive,analgesia,anti-oxidant,anti-inflammatory,pesticides,herbicides,antiviral,anticancer,etc.We take the Trx inhibitors PX-12 as the lead compound,18 substituted disulfdes-1,2,4-triazole derivatives were designed and synthesized.By using the method of CCK-8,we estimated the proliferation inhibitory activity of these compounds on three tumor cells of A549,Hela and SMMC-7721.We take 5-fluorouracil for comparison.For A549 cells,in addition to the compound 14 g,the other compounds showed good proliferation inhibition activities,with IC50 values ranging from 2.79 to 13.38 ?mol/L.Twelve of these compounds displayed higher activities than the positive control5-fluorouracil(IC50=8.13?mol/L).Especially noteworthy is compound 13 d,which showed the most significant antiproliferative activity with IC50 value of 2.79 ?mol/L.For Hela cells,Except compound 13 a,14f and 14 g,the other compounds revealed stronger antitumor activity,with IC50 values ranging from 3.51 to 7.75 ?mol/L.Fifteen of these compounds showed better effect than the control 5-fluorouracil(IC50=17.21?mol/L).Particularly outstanding is compound 13 f,which displayed the best antiproliferative activity with IC50 value of 3.51 ?mol/L.All the target compounds displayed good proliferation inhibiton activities against SMMC-7721 cells,with IC50 values ranging from 2.97 to 6.62 ?mol/L.Seventeen of these compounds showed higher activities than the positive control 5-fluorouracil(IC50=5.62?mol/L).Especially prominent is compound 14 c,which showed the most significant antiproliferative activity with IC50 value of 2.97 ?mol/L.In summary,the 18 new synthesis compounds,which combine the disulfide and1,2,4-triozole structures,showed different proliferation inhibition effect against three tumor cells.Some of the target compounds displayed better activity than the contrast 5-fluorouracil.These results laid a foundation for further research.