Design,Synthesis And Antitumor Activity Evaluation Of Sulfamide-1,2,3-triazole Derivatives

Sulfonamide compounds were a class of small synthesized molecular compounds with simple structures,extensive biological activities and high safety.Sulfonamide compounds were first used as antibacterial agents in clinical application,then its anti-inflammatory,antiviral,antitumor and other activities been reported.Recently,with the application of click chemistry,1,2,3-triazole compounds were acted as linker group connected to other active fragments because of its potent antitumor activity.Based on the research above,in order to find a higher effective and lower toxin agent,in this article we will use the sulfonamide compounds as the nucleus group,connect with 1,2,3-triazole and introduce some other functional groups on 1,2,3-triazole's C-4 position.Finally,we designed and synthesized series of sulfonamide derivatives,evaluated their antitumor activity in vitro and the structure-activity relationship analysis.The main research work is as follows:Firstly,through the diazotization reaction,nucleophilic substitution,click chemistry and other organic reactions,we finally synthesized six series of 46 sulfonamide-1,2,3-triazole derivatives: sulfonamide-1,2,3-triazole-dithiocarbamate derivatives,sulfonamide-1,2,3-triazole-sulfanilamide derivatives,sulfonamide-1,2,3-triazole-sulfurheterocycle derivatives,sulfonamide-1,2,3-triazole-arylamine derivatives,sulfonamide-1,2,3-triazole-nitrogen-containing benzoheterocycle derivatives,sulfonamide-1,2,3-triazole-coumarin derivatives.All of them were verified by 1H NMR,13 C NMR and MS,and are new compounds that not been reported.Secondly,we selected human gastric cancer cell line MGC-803,human esophageal cancer cell line EC-109,human prostate cancer cell line PC-3 to evaluate all compounds' antitumor activity,and summarized the structure-activity relationship.The result shows that most of the sulfonamide-1,2,3-triazole derivatives showed good antitumor activity for one or three cancer lines.For example,the first series of compounds selected to inhibit the PC-3,the second,third,sixth series of compounds display their inhibitor on MGC-803,and the rest exhibit broad-spectrum antitumor activity.In conclusion,we synthesized 46 new sulfonamide-1,2,3-triazole compounds with simple approach and all compounds have never been reported.The 2C,3G,6C could be used as lead compounds for their good antitumor activity,they worth a further study and provide the direction for further study.