Synthesis And Inhibition On Hela Cell Of Ursolic Acid Derivatives

Ursolic acid, a pentacyclic triterpene acid, which exists abundantly in the plant kingdom,exhibits various biological activities, such as antitumor, hepatoprotective and anti-inflannatory.In order to search for ursolic derivatives with high antitumor bioactivities, a series of ursolic acidderivatives were synthesized.Six ursolic acid derivatives modified at the C-3position were designed and synthesized byoxidation, oximation or hydrazonation from ursolic acid, the structures of the compounds wereidentified by IR,1H NMR,13C NMR and MS, in which four of them are new compounds. Theinclusion complexs of ursolic acid-β-cyclodextrin and ursolic acid derivatives-β-cyclodextrinwere prepared by saturated water-solvent method, and were characterized by IR. Thecytotoxicity of ursolic acid and its derivatives against the HeLa cell was detected by MTTcolorimetric assay in an attempt to develop potent antitumor agents.The inhibition of ursolic acid and its derivatives on HeLa cell was enhanced with theincreasing of the time, the effect was time dependent. The inhibition was enhanced with theincreasing of the concentration in a certain degree of concentration, the effect was dosedependent.3-Oxime-ursolic acid and3-(4’-nitrophenyl)-hydrazone-ursolic acid had stronger cellgrowth inhibitory than ursolic acid and5-FU on HeLa cells, the IC50values of them were8.3μg/mL and23.5μg/mL, respectively.3-Oximino-ursolic acid had the highest activity on HeLacell, and the inhibition rate was98.9%.3-Oxo-ursolic acid and3-(2’,4’-dinitrophenyl)-hydrazone-ursolic acid had a similar inhibition on HeLa cell line.3-(2’-Nitrophenyl)-hydrazone-ursolic acid had the weakest inhibition activity, followed by3-(3’-nitrophenyl)-hydrazone-ursolic acid. The above four compounds had weaker cell growthinhibitory than ursolic acid. The inclusion complexs of ursolic acid-β-cyclodextrin and ursolicacid derivatives-β-cyclodextrin hadn’t significant inhibition.