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.

Synthesis and anti-tumor activity of derivatives of ring A of asiatic acid.

Based on the simulation of the docking of survivin protein with known small molecule inhibitors, the active groups which can bind to target proteins were analyzed by the techniques of computer-aided drug design (CADD). These active groups were introduced into the A-ring of asiatic acid and their C-28 sites were reconstructed simultaneously. Ten asiatic acid derivatives were designed and synthesized, and their structures were confirmed by MS and NMR. The inhibitory activities of the asiatic acid derivatives against HepG2 and SGC7901 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The results showed that compounds I6 and II4 exhibited more potent cytotoxicity than the positive control drug gefitinib, which was comparable to that of adriamycin.[Formula: see text].

Design, synthesis, and antitumor activity of oleanolic acid derivatives.

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.

Synthesis and antitumor activity evaluation of novel oleanolic acid derivatives.

Ten novel oleanolic acid (OA) derivatives were synthesized through modifications at positions of A ring and C-28. Inhibitory activities of the oleanolic acid derivatives against SGC7901 and A549 cell lines were evaluated and confirmed by the tetrazolium bromidesalt (MTT) assay. The lab results revealed that all these compounds displayed some antitumor activity against SGC-7901 and A-549 cell lines. Among them, II4 and II5 exhibited excellent antitumor activities against SGC7901 cells and A549 cells, compared with gefitinib. Molecular docking studies have shown that compounds II4 and II5 produce potent antitumor activities by interacting with C-kit receptor through hydrogen bonds and hydrophobic bonds.