Synthesis And Antitumor Activities Of 5-hydroxy-3-(4'-nitropheny1)-7-substitued-benzopyran-4-one

Recent years studies have shown that Genistein,a nature isoflavone found in soy,has antitumor effects on breast tumor in vivo and vitro and antiproliferation activities against lung and prostate cancer cells in vitro. The main mechanism is that Genistein is a tyrosine protein kinase inhibitor. Genistein inhibits DNA topo isomerase II,cell cycle-related proteins,angiogenesis,express of some oncogenes,progression and invasion of cancer cells in vitro and vivo,and induce cells apoptosis and differentiation,too. Genistein is a good leading compound for antitumor agents.According to studies on Genistein and its structure-activity relationships,30 of genistein derivatives of 5-hydroxy -3-(4'-nitrophenyl)-7-substitued -benzopyran-4-one were synthesized,28 of them were first reported. All the title compounds were tested their antitumor activities on breast cancer cell line MDA-MB-435 and prostate cancer cell line TSU using the method of 3H-TdR incorporation assay in vitro. A majority of the title compounds have antitumor activities,among them,compound E2 has a potent antitumor effect on MDA-MB-435 cell line with ICso 6mg/L,and compounds A2 and A3 have potent antitumor effects on TSU cell line with ICso 2mg/L. Further study on mechanism and antitumor activities in vivo is now underway. The structure-activities relationships were discussed,and the models of compounds binding with target enzyme were presumed.