Synthesis And Anti-tumor Activity Of Derivatives Of Ursolic Acid

Cancer has become one of the most serious diseases threatening human life,health and life.Some natural active ingredients have been used in the diagnosis and treatment of antitumor disease.For example,paclitaxel,camptothecin,vincristine,etc.Ursolic acid is widely distributed in a variety of natural plants,with a variety of biological activity.In recent years,researchers in pharmacological research found that UA can act on different stages of cancer,which is the NF-κB pathway to determine the inhibitory effect of ursolic acid as the lead compound,pharmacophore model,a novel structure and virtual screening small molecule active prominent inhibitors,and the optimization of synthetic small molecule inhibitors screening,screening preliminary anti-tumor activity.Ursolic acid as the starting material,we designed and synthesised 18 compounds of three series.Firstly,C-3 hydroxy ursolic acid with Jones reagent,further introduced carbonyl at alpha site,got 2,3-dicarbonyl ursolic acid,then 28 carboxyl esterification reaction,and finally obtained the first Ⅰ₁^Ⅰ₆ phenylhydrazine reaction compounds;or reaction with 4-picrylhydrazyl second compounds Ⅱ₁^Ⅱ₆;or reaction with 4-chloride third phenylhydrazine hydrochloride compound Ⅲ₁^Ⅲ₆.All compounds in the reaction process using TLC detection reaction end point,its structure through MS,¹H-NMR to be justified.MTT method was used in this paper,human hepatoma cells lines（BEL-7402）and human gastric cancer cells lines（SGC-7901）as indicators of as cytotoxic activity in vitro pharmacological evaluation and choose adriamycin and VP-16 as the positive control.The results showed that the inhibitory rates of the target compounds on the two cell lines were significantly higher than that of the parent compound,and the IC₅₀0 values of the compounds Ⅱ₄,Ⅲ₄ and Ⅲ₆ to BEL-7402 were 7.08,5.63 and 3.49μM,respectively,and The IC₅₀0 values of the compounds Ⅱ₆,Ⅲ₄ and Ⅲ₆ to SGC-7901 were 6.30,8.73 and 7.01μM,respectively.The IC₅₀0 values of compounds Ⅱ₄,Ⅱ₆,Ⅲ₄ and Ⅲ₆ were comparable to or stronger than the positive control drugs,which deserved further study.