Synthesis And Antiproliferative Evaluation Of Novel 1,2,4-triazole Disulfide Derivatives Bearing Urea Moiety

Among various human diseases,therioma have proven to be one of the most horrible diseases that cause of death in the world.In the current phase of clinical research,surgery is the first choice,but surgery brings a lot of risks and even complications.Therefore,chemical medicine therapy method is the hot point of medical research,finding new and effective treatment methods and targets is very important.Relevant experiments show that a thioredoxin system is comprised by thioredoxin（Trx）,thioredoxin reductase（TrxR）and nicotinamide adenine dinucleotide phosphate（NADPH）.Studies have shown that Trx is closely related to tumor cells such as hyperplasia.This system has already become a novel attractive target for development of new cancer treatment as well as.Disulfide derivatives regard as an important sulfur compounds,showed a large number of activities,such as anti-cancer,anti-inflammatory,anti-bacterial,anti-convulsive and other biological activities.Among them the anti-tumor features attract great interests from medicinal chemists.Triazole is consists of two carbon atoms and three nitrogen atoms,which make up of five heterocyclic ring.And it also convey massive pharmacological activities,such as anti-bacterial,anti-convulsive.It has become an important structure among the drug design.Based on the important biological significance of 1,2,4-triazole and disulfide derivatives,this paper designed and synthesized benzene derivatives with benzene 1,2,4-nitrazotriazole disulfide derivatives of urea moiety.The whole newly compounds were characterized by IR,¹H NMR,¹³C NMR and High Resolution-Electrospray Ionization-Mass Spectrometer（HR-ESI-MS）.1-methylpropyl 2-imidazolyl disulfide（PX-12）and 5-fluorouracil（5-FU）were regard as positive controls,the CCK-8 method was used.We evaluated for all the compounds proliferation inhibitory activities against human cancer cell lines A549,Hela,SMMC-7721and normal cell line L929.The bioassay results showed that all tested compounds showed antiproliferaten with different degrees against the three tumor cancer cell lines.In A549 cell line,the majority of them exhibited better activities than positive control PX-12 and 5-FU,especially compound7g,7d,9c and 9d exhibited the best antiproliferative activity with IC₅₀ value of 2.13,3.68,3.27 and 2.69μmol/L;In Hela cell line,all the compounds displayed inhibition effect with different degrees.Compound 9a,9c and 9d showed the best anticancer activity than positive controls with IC₅₀ value of 3.31,4.45 and 4.77μmol/L;In SMMC-7721 cell lines,some of the compounds exhibited better effects than PX-12 and 5-FU.Among the compounds 9f and 9k showed the highest effective biological activity with IC₅₀ value of 1.68,1.10μmol/L;In L929cell line,comparing with PX-12 and 5-FU,most compounds displayed week cytotoxic effect.Briefly,28 target compounds showed different levels of inhibition activities against three different tumor cells,and most of compounds exhibited weak cytotoxicity against the normal cell line L929.Therefore,the results may laid the structure-function relationship and action mechanism research of this series of compounds.