Study on the modification and anti-tumor activity of silybin derivatives for CDK4/6 targeted / 药学学报

By using computer-aided drug design, the activities group model which CDK4/6 inhibitors on the market were introduced to silybin C-7, and a series of silybin derivatives were designed and synthesized, and the structure was confirmed by MS, 13C NMR and 1H NMR. The in vitro antitumor activity evaluation of the target compound was carried out by MTT method, and the in vitro anti-tumor activity was carried out in human hepatocellular carcinoma cells (HepG-2). Experimental results show that all compounds are higher than the activity of the parent silybin, of which compound I1 has a certain inhibitory effect on human HepG-2 cells, which is worth further study.

Targeting PDGF receptor inhibitors: synthesis and biological evaluation of oleanolic acid analogs / 药学学报

The computer-aided design was used to simulate the docking of PDGF receptor with known active compounds, and the active groups that can bind to key sites were identified by analyzing the key amino acid residue fragments that exerted active effects on the target proteins. The natural product oleanolic acid was used as the parent, and the active group was introduced into the 2-position, and the C-28 carboxyl group was esterified and amidated. A series of oleanolic acid analogues targeting PDGF receptor inhibitors were designed and synthesized. Their structures were confirmed by MS and NMR. Through MTT assay, SGC-7901 and A549 cells were selected for preliminary in vitro anti-tumor activity screening. PDGF receptor protein inhibition test was performed on I3 and Ⅱ5 by FPIA. The activity tests showed that I3 and Ⅱ5, compared with the positive control drug, had stronger inhibition. FPIA test showed that Ⅱ5 and PDGF receptor protein had good binding ability. The newly synthesized oleanolic acid analogues have significantly higher antitumor activity than the parent compound and deserve further study.

Synthesis and biological evaluation of oleanolic acid analogs based on survivin target / 中国药学杂志

OBJECTIVE: To design and synthesize a series of oleanolic acid analogs posessing anti-tumor activity based on survivin target. METHODS: 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 fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through using the natural product, oleanolic acid, as a lead compound, the active groups were introduced onto its A-ring, and the carboxyl group at the C-28 position was modified using amidation. SGC-7901 and A549 cells were used to screen the antitumor activity in vitro through the standard MTT method. RESULTS: Ten new oleanolic acid derivatives were designed and synthesized,and their structures were confirmed by MS and NMR. The compounds 5 and Ⅱ5 exhibited more potent cytotoxicity than the positive control drugs. CONCLUSION: The novel oleanolic acid analogues have better antitumor activity than the parent compound, which are worthy of further study.