Using the techniques of computer-aided drug design, the docking of survivin and known active small molecules was simulated and then the key amino acid residue fragments of the target protein were analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, oleanolic acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, 20 new oleanolic acid derivatives had been designed and synthesized. HepG2 and SGC-7901 cells were used to screen the antitumor activity through the standard MTT method. The compounds, II3, III5 and IV4, exhibited more potent cytotoxicity than positive drugs. Western blot experiment demonstrated that compound II3 can effectively inhibit the proliferation of HepG2 cells.
Keywords: Oleanolic acid derivatives; antitumor activity; molecular docking; synthesis.