Synthesis And Evaluation For The Anticancer Activity Of Oleanolic Acid Derivatives

Natural products and their derivatives have been was the main source of innova-tive drug, it is also an important tool for biomedical research. More than 50% of the clinical drugs are derived from natural products. Therefore, the synthesis of natural products which are of important biological functions and mechanisms of biological research has the vital significance. We have efficiently synthesized several aminoacyl derivatives of oleanolic acid and explore their underlined mechanism of pro-apoptotic towards Hela cells. When we converted 28-COOH into aminoacyl group and then introduced other groups, obtained derivatives showed distinct activities. By "simple" modifications of OA showing increased ability to induce apoptosis targeting Hela as a function of structural amidation than analogous R group esterification modification, ideal IC50 values have been reported. The results inspired us the addition of basic and ionizable group such as amino to triterpene skeletons may be an effective way to en-hance the anti-tumor activity. Overall, this scaffold provided several compounds with inhibition activities com parable to or better than that of the parent drug OA.The underlined mechanism of pro-apoptotic effects towards Hela cells was also discussed. OA and its derivatives induced S and G2/M-phase cell cycle arrest. The trigger of cell apoptosis by OA or its derivatives is characterized by distinct biochem-ical and morphological features due to different R group, such as plasma membrane blebbing, cell shrinkage. In this study, we found that the compounds accelerated ROS enrichment and and increased Bax/Bcl-2 ratio, both of which could explain the de-creased of △Ψm. Moreover, they integrate death signals through Bcl-2 family mem-bers and coordinate caspase activation caspase-3, an effector caspase of apoptosis. Structure-activity dates of OA and its derivatives with various aminoacyl groups have greatly enhanced our understanding to develop these potential drug candidates design targeting Hela cells, particularly in view of their relationship to the more traditional carbopolycyclic scaffolds. Results suggested that the acylamino would provide better foundation for further optimization. More importantly, the point of modification like amidation can tolerate a variety of functional groups such as amine, sulfhydryl, nitro, halogen groups and acidic or basic group, thus opened the opportunity for further op-timization for the triterpenoid scaffolds.