Design,Synthesis And Bioactivity Evaluation Of Z-2,3-diaryl Acrylonitrile And Thiazolo Triazolone Derivatives

Cancer is a malignant disease that threatens human health.In China alone,2 million people died of cancer each year.At present,the way to cure cancer is surgical treatment.But many kinds of cancer can not be operated such as leukemia,lymphoma cancer.Because the tumor cells have eroded the surrounding tissue or spread around the body.Chemotherapy is greatly harmful to body,so many cancer patients not only bear the pain of the tumor itself,but also the damage caused by chemotherapy drugs.Therefore,to find the drugs with high antitumor activity and low toxicity to normal cells is a common problem faced by scholars around the world.In this paper,we found that resveratrol extracted from plants has antibacterial,anti-inflammatory and anti-tumor properties.But because of its structure,it contained three hydroxyl structures,which caused poor self-stability and low activity.Therefore,2,3-diaryl acrylonitrile compounds were synthesized by methylation and introduction of cyano group using resveratrol as a lead compound,and detected the anti-tumor activity by MTT assay.According to the literature,nitrogen-containing heterocyclic structure is a kind of heterocyclic ring which binds to the organism easily.Among them,1,2,4-triazole is also a kind of important anti-tumor active group.The two groups was conjugated as bridge bond to synthesize some triazole and thiazolone derivatives and to detecte the anti-tumor activities.All compounds were charactered by ¹H NMR,IR,and ¹³C NMR.The results showed that 2,3-diarylacrylonitrile compounds had good antitumor activity.Among them,the antitumor activity of 4d[?Z?-3-?4-bromophenyl?-2-?3,5-dimethoxyphenyl?acrylonitrile]and 4p[?Z?-2-?3,5-dimethoxyphenyl?-3-?4-ethoxyphenyl?acrylonitrile]against HeLa cell was stronger than that in paclitaxel and had lower toxicity against normal cell L-02,showing selective inhibition activity.The compounds can effectively arrested the HeLa cells in G2/M phase.Triazole and thiazolidone derivatives also showed different degrees of anti-tumor activity.Among them,5k[?Z?-5-?3-?2-oxopropyl?benzylidene?-2-?pyridin-3-yl?thiazolo[3,2-b][1,2,4]triazol-6?5H?-one]had the best activity,especially against AGS cells with the IC50 value of 20.3 ? 8.3,which is an effective anti-tumor compound.