The Design,Synthesis And Antitumor Activity Of Ursolic Acid Derivatives

A series of human health harmed severely by malignant tumors.In recent years,natural products are an indispensable field in anti-tumor.The natural products of ursolic acid has effective anti-tumor pharmacological activity and multiple mechanisms of action.In different stages,prevention and inhibition showed various degree.Based on the previous work of our research group,we used UA as the leading compound and constructed small molecule inhibitors of the protein kinase by computer-aided drug design18 UA analogues were designed and 15 derivatives successfully synthesized.Respectively,at the C-3 position linked alkanoyloxy,C-11 double bond to ketone,C-28 position link different amines.Finally,15 compounds I1 to I15 were obtained.Theirreaction checked by TCL and the crude purified by colummn chromatograhy on silica gel using prtoleum ether and ethyl acetate(（V/V）as eluent.The structure of the compounds was confirmed by MS and 1H-NMR.Their activities againstSGC7901and HepG2 cellsweretestedby MTT assay.Importantly,The results showed that compounds I₂ and I₅ proved to be the most active compound among all tested derivatives.The inhibitory rates of compound I₂ on SGC7901 and HepG2 cells were 47.61%and50.58%,respectively,and their IC50 values were 10.32 and 8.79μmol/L,respectively.The inhibitory rates of I₆ on SGC7901 and HepG2 cells were 49.68%and 45.76%13.87 and 12.23μmol/L,Their activity show especially more inhibitory activity on these cells than that of commercially acailable drug paclitaxel.Therefor,this article has certain reference value for the research on the structural modification of ursolic acid and p ent acyclic triterpenoids.