芹菜素醚化及溴化衍生物的合成及抗肝癌活性研究

Synthesis and Anti-hepatoma Activities of Apigenin etherified and brominated derivatives

目的:合成芹菜素甲醚化、二氟甲醚化及溴化衍生物,进行抗肝癌活性研究。方法:以芹菜素为原料,经硫酸二甲酯甲醚化、溴素溴化或一氯二氟甲烷二氟甲醚化,柱层析分离,合成芹菜素衍生物。MTT法测定氟尿嘧啶(5-FU)、芹菜素衍生物对体外培养人肝癌HepG2细胞活性的抑制作用。结果:共得到6个化合物,结构经1H-NMR等进行了确证;MTT法测定结果表明,化合物1抑制HepG2细胞活性作用的IC50值是7.86±1.35μg/mL,与化疗药5-FU(7.18±0.85μg/mL)类似;化合物2～7的IC50值分别为2.62±0.32、0.65±0.12、3.21±0.43、4.36±0.51、4.13±0.46和1.96±0.29μg/mL;其中以化合物3的效价强度最大,是先导物芹菜素的12.09倍,化疗药5-FU的11.05倍。结论:芹菜素衍生物的抗肝癌活性较芹菜素更强,其中化合物3(6-8-二溴-7,4'-二甲氧基-5-羟基黄酮)是一个具有开发潜力的抗肝癌活性新化合物。

Objective To synthesize a series of apigenin etherified and brominated derivatives and study their anti-hepatoma activities.Methods Apigenin derivatives were prepared by apigenin through methoxylation,difluoromethoxylation or bromination,their inhibitory effects in human hepatocellular carcinoma HepG2 cells in vitro were were measured by MTT assay.Results Six compounds were prepared and their structures were authenticated by 1H-NMR.MTT assay showed that the IC50 of compound 1 was 7.86±1.35μg/mL,it was similar to 5-FU(IC50=7.18 ± 0.85μg/mL) .IC50 of compounds 2-7 were 2.62±0.32,0.65±0.12,3.21±0.43,4.36±0.51,4.13 ±0.46 and 1.96 ±0.29 μg/mL.among these derivatives,compound 3 showed the strongest activity against HepG2 cells in vitro,it was 12.09 times of Apigenin,11.05 times of 5-FU.Conclusion Six apigenin etherified and brominated derivatives had more effective antitumor activity than apigenin.compound 3(6-8-dibromo-7,4 '-dimethoxy-5-hydroxyflavone) showed the strongest activity against HepG2 cells in vitro,it was a potential new compounds for anti-hepatoma.