Study on synthesis and biological activities of quercetin-3-O-amide derivatives / 中草药

ABSTRACT

Objective: To design and synthesize quercetin amide derivatives and study the antitumor activity of these compounds in vitro. Methods: The cheap rutin was used as the raw material, the benzyl group was selectively protected, the Williamson was converted into ether, and then the target product was obtained by the hydrogenation debenzylation of Pd/C catalyst. The antioxidant activity of the target compound was investigated by the DPPH method. The inhibitory effects of the target compounds on the proliferation of human esophageal squamous cell carcinoma cell EC109, human esophageal squamous cell carcinoma cell EC9706, human gastric cancer cell SGC7901, and mouse melanoma cells B16-F10 were investigated by MTT method. Results: The structures of the 15 quercetin amide derivatives were confirmed by 1H-NMR, 13C-NMR, and ESI-MS. The antioxidant results showed that the SC50 of most target compounds was smaller than or equivalent to quercetin, which suggests that 3-OH is not an essential group for the antioxidant activity of quercetin. The results of anti-tumor experiments showed that after the structural modification of quercetin by chemical methods, its anti-tumor activity was significantly enhanced in vitro. Among them, the inhibitory effect of compound 7-6 on EC109 (IC50 = 10.25 μmol/L) is significantly better than that of the parent drugs quercetin (IC50 = 31.884 μmol/L) and 5-FU (IC50 = 41.738 μmol/L). Potential new antitumor candidate compounds. Conclusion: The 15 quercetin-3-O-amide derivatives are all new compounds. Among them, compounds 7-6 have good antitumor activity and deserve further study.