To discovery novel VEGFR inhibitors, 12 novel asiatic acid derivatives were designed by computer-aided drug design (CADD) technology. Then, these novel asiatic acid derivatives were synthesized by introducing active groups at ring A and C-28 positions of asiatic acid. The structures of these novel analogues were confirmed by NMR and MS. Moreover, the anti-tumor activities of these novel asiatic acid derivatives on human hepatoma cells HepG2 and human gastric cancer cells SGC7901 were evaluated by MTT assay. As a result, compounds I2 and II4 showed stronger cytotoxicity on tumor cells than asiatic acid and positive control drugs such as gefitinib and paclitaxel. In conclusion, our study synthesized twelve novel asiatic acid derivatives and determined compounds I2 and II4 had better anti-tumor effect which may be potential candidate compounds for tumor therapy.
Keywords: Asiatic acid derivatives; anti-tumor activity; molecular docking.