Synthesis And Antitumor Activity Of Furazan Nitrogen Oxides And Benzophenone Analogues

Benzophenones can induce tumor cell apoptosis by inhibiting tubulin polymerization,which is a potential research direction of anti-cancer.As a nitric oxide donor,furazan nitric oxide can provide high concentration of nitric oxide（NO）to inhibit the proliferation and migration of tumor cells.Furazan nitrogen oxides and Benzophenones showed synergistic effects on tumor cell inhibition and killing.Based on the splicing principle,we selected suitable Linker to splice Furazan nitrogen oxides and benzophenone,and studied the structure-activity relationship in the anti-tumor aspects.Our research group designed and synthesized 26 benzophenones and characterized them by ¹H-NMR and ¹³C-NMR.The results showed that most of the compounds had certain anti-proliferative activity against four kinds of tumor cells,including A2780.Among them,compound I-4 was found to have the strongest activity against four types of cancer cells,with IC₅₀values ranging from 8 to 15 n M.Further mechanism studies showed that compound I-4 could induce tumor cell cycle arrest and promote apoptosis,thus producing a killing effect on tumor cells.Compound I-4 has also been shown to inhibit angiogenesis by preventing tubulin from aggregating.Compound I-4 has also been shown to significantly inhibit tumor growth in vivo using xenograft mouse models.The experiment also provides a new way of thinking and direction for the study of the inhibitory effect of benzophenone and furazan nitrogen oxides on tumor.