Synthesis and Biological Activities of Quercetin Amide Derivatives / 中国药学杂志

ABSTRACT

OBJECTIVE: To synthesize the quercetin amide derivatives and determine their biological activities. METHODS: Quercetin was used as a precursor whose hydroxyl group on 3-C of C ring was modified selectively. Using rutin as raw material, 13 quercetin amide derivatives were obtained by selective protection of benzyl group, Williamson ether reaction, amidation reaction and Pd/C catalytic hydrodebenzylation. The antioxidant activity of 13 target compounds was investigated by DPPH method. In addation, MTT assay was performed to investigate the proliferation-inhibition effects of these quercetin derivatives on the proliferation of human esophageal carcinoma cell line EC109, human esophageal carcinoma cell line EC9706, human gastric cancer cell line SGC7901 and mouse melanoma cell line B16-F10. RESULTS: The chemical structures of the target compounds were confirmed by IR, 1H-NMR, 13C-NMR and ESI-MS. Antioxidant experiments showed that the values of SC50 of most target compounds were less than or comparable to quercetin, indicating that 3-OH is not an essential group to maintain the antioxidant property of quercetin. Moreover, antitumor activity experiments showed that the anti-tumor activity of quercetin amide derivatives was enhanced. Among them, the inhibition effect of compound 7-13 on EC109 (IC50=10.25 μmol•L-1) was significantly outperformed the parent drug quercetin (IC50=31.884 μmol•L-1) and 5-FU (IC50=41.738 μmol•L-1), which is a very promising novel anti-tumor candidate compound. CONCLUSION: After structural modification of quercetin by chemical methods, the antioxidant activity is comparable to that of quercetin, and the antitumor activity in vitro is significantly enhanced.