Design, synthesis, and anti-tumor activity of derivatives of ring A and C-28 of asiatic acid.

Based on computer-aided drug design (CADD), the active groups of the known active small molecule compounds that can bind to EGFR target protein were analyzed through the molecular docking method. Then, 12 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 compounds were determined by NMR and MS. Furthermore, the anti-tumor activities of these derivatives on human lung cancer cells (A549) and human breast cancer cells (MCF-7) were evaluated by MTT assay. In conclusion, compounds I4 and II3 have stronger anti-cancer activity than parent compounds, the activities were stronger than gefitinib and comparable to afatinib, which may be potential candidate compounds for tumor therapy.

Design, synthesis, and antitumor activity of novel oleanolic acid analogues targeting EGFR.

Based on the simulated docking of Epidermal growth factor receptor inhibitors with known active small molecule compounds, computer-aided drug design technology was used to analyze key amino acid fragments and determine the active groups binding with key sites. Then, twelve novel analogues of oleanolic acid (OA) were synthesized by introducing active groups at the C-3 and C-28 positions of OA. The structures of these novel analogues were confirmed by NMR and MS. Furthermore, the antitumor activities of these novel analogues were evaluated by MTT assay. As a result, compounds I3 and II3 showed stronger cytotoxicity on tumor cells than positive controls. In conclusion, our study synthesized twelve novel analogues of OA and determined compounds I3 and II3 had better antitumor effect, which may be potential candidate compounds for tumor therapy.

Synthesis and anti-tumor activity of asiatic acid derivatives targeting VEGFR.

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.

Design, synthesis and anti-tumor activity of asiatic acid derivatives as VEGF inhibitors.

The VEGF receptor is mock-coupled with a known active compound and the active groups of the inhibitor which can bind to VEGF were analyzed. Using asiatic acid as a lead compound, 10 novel skeleton candidate compounds were designed through introduction of the active groups onto the special location and synthesized simultaneously. Furthermore, the structure of these compounds was determined by 1H NMR, 13C NMR and MS and 9 compounds were identified as the new compounds. Moreover, the in vitro anti-tumor activities of these new compounds were determined by MTT assay on two cancer cell lines (HepG2 and SGC-7901). The results showed that compounds I1 and II2 have more potent anticancer activity than positive control drugs such as gefitinib and paclitaxel.