Synthesis And Inhibition On Liver Cancer And Lung Adenoma Cell Line Of Oleanolic Acid And Ursolic Acid Derivatives

Six oleanolic acid and ursolic acid derivatives were synthesized by oxidation, oximation or hydrazonation from oleanolic acid and ursolic acid.The antitumor activities of eight compounds on SMMC-7721 human hepatoma and lung adenoma cell line LTEP-α-2 were investigated by MTT colorimetric assay. The results showed that all compounds had significant antitumor activity. The inhibition was enhanced with the increasing of the concentration in a certain degree of concentration, and the effect was time-dependent.Oleanolic acid and its derivatives had a similar inhibition on SMMC-7721 human hepatoma and lung adenoma cell line LTEP-α-2. The inhibition of Oleanolic acid on the cells was similar with 3-oxo-oleanolic acid, which were more effective than 3-oximino oleanolic acid and 3-(2, 4-dinitrophenyl)-hydrazone oleanolic acid.Ursolic acid and 3-oximino ursolic acid had a similar inhibition on SMMC-7721 human hepatoma which was more effective than other oleanolic acid derivatives, and the IC50 values of Ursolic acid and 3-oximino ursolic acid were 3.8μg/mL and 4μg/mL, respectivily. 3-Oximino ursolic acid had the highest activity on lung adenoma cell line LTEP-α-2, IC50 was 7.4μg/mL. 3-(2, 4-Dinitrophenyl)-hydrazone ursolic acid was the weakest inhibitor of the two cell lines.Microbial transformation of Oleanolic acid by Fusarium avenaceum afforded a lactone derivative of Oleanolic acid. The biotransformation products were separated on silica gel column chromatography, and the characterization of the metabolite was performed by 2D NMR spectroscopic methods.