Objective To design and synthesize a series of chrysin derivatives and evaluate the antitumor activities with MTT assay, so as to investigate molecular structure-activity relationship with molecular docking. Methods Target products were synthesized with high yield by substitution reaction, hydrolysis reaction, esterification reaction, and saponification reaction in sequence, and activities of all compounds were evaluated with human gastric carcinoma cell lines MGC-803 and human breast carcinoma cell lines MCF-7 through standard MTT assay. Molecular docking results were calculated with Surflex Geom X programme of Sybyl X-2.0 version workstation. Results 7-O-amino acids chrysin derivatives 6a-6l were synthesized and their inhibitory effects were evaluated by comparing the material chrysin with positive control drug 5-fluorouracil (5-FU). Among these derivatives, compound 5b (IC50 = 24.50 ± 2.26 μmol/L), 5k (IC50 = 24.30 ± 2.19 μmol/L), and 6f (IC50 = 24.61 ± 2.01 μmol/L) showed better inhibitory activities against MGC-803 cell lines, and compound 5g (IC50 = 13.15 ± 1.73 μmol/L) and 5j (IC50 = 12.34 ± 1.25 μmol/L) showed better inhibitory activities against MCF-7 cell lines than chrysin and 5-FU. Molecular docking scores showed a credible consistency compared with MTT results. Conclusion Compounds 5b, 5d, 5g, 5j, 5k, and 6f showed good antiproliferative effects on specific tumor cells, and compound 5g should be researched further when according to molecular docking.
关键词:
氨基酸白杨素衍生物;抗肿瘤;分子对接;合成
Keywords:
Project Supported:
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study (No. 2014-405) and Hunan Provincial Department of Education Project (14C1003)
Ding Liu, Yan-peng Li, Hong-xiu Shen, Yang Li, Jun He, Qi-zhi Zhang, Yun-mei Liu . Synthesis and anti-tumor activities of novel 7-O-amino acids chrysin derivatives[J]. Chinese Herbal Medicines (CHM),2018,10(3):323-330
