Résumé
Objective: To synthesize 8-substituted quercetin derivatives and test their cytotoxicity on human cancer cell lines, so as to find out hit or lead compounds via structure activity relationship(SAR)analysis. Methods: Using rutin as the raw material, quercetin was obtained by the acid hydrolysis of rutin, and the 8-substituted quercetin derivatives, 3a-3h, were synthesized via the whole hydroxyl protection of quercetin and then halogenation, followed by the Suzuki coupling or heck coupling reaction. The in vitro inhibitory activity of these derivatives was assayed by the MTT method using human cancer HepG2, HT-29 and K562 cell lines. Results and Conclusion: Eight new target compounds, 3a-3h, were synthesized, and their structures were confirmed by the 1H NMR, 13C NMR and MS data. The inhibitory effect of 3b-3h on HepG2 cell line, 3b and 3d on HT-29 cell line, and 3b-3d and 3f-3h on K562 cell line has remarkably and significantly enhanced than that of quercetin, and the present research results provide a suggestive preliminary SAR.
Résumé
Quercetin has the effects of anti-oxidation, prevention of cardiovascular and cerebrovascular diseases, chemical prevention, and anticancer. Because of the low bioavailability, poor water solubility, rapid metabolism, and enzyme degradation, its clinical application is limited. Due to the good solubility, high bioavailability, stable metabolism, and little the poisonous side effects, quercetin derivatives are the hot spots of the study on the modification of quercetin structure. In the last 10 years, researchers have synthesized a large number of quercetin ethers, esters, metal complexes, C-4 carbonyl oxygen substituted derivatives, and A, B ring modified compounds, and the detection of anticancer activity was conducted in vitro. In this paper, the anticancer activity of quercetin derivatives in recent 10 years is reviewed.