Synthesis and Anti-Tumor Activity of Oleanolic Acid Derivatives

With the computer drug-aided design and the key amino acid residue fragment of the target protein analyzed on the basis of simulated docking of Survivin and known active small molecules, the active groups capable of binding to the critical sites were determined. After the natural product Oleanolic acid was used as lead compound, then the active groups were introduced on the ring of A, next the carboxyl group at the C-28 position was modified by esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized. SKOV3 and BGC-823 cells were used to screen the antitumor activity in vitro through the standard MTT method. Among the selection, compounds II₃、III₅ and Ⅳ₄ exhibited more potent cytotoxicity than positive drugs.