2,3,4-三甲氧基查耳酮类衍生物的合成及体外抗宫颈癌活性研究

Synthesis of 2,3,4-trimethoxychalcone derivatives and anti-cervical cancer activity in vitro

目的研究以甘草查耳酮B为先导化合物合成的3个查耳酮类衍生物的体外抗宫颈癌活性、对宫颈癌细胞增殖周期的影响及促凋亡作用。方法以取代苯乙酮和取代苯甲醛为原料,通过Claisen-Schmidt反应合成2,3,4-三甲氧基查耳酮类衍生物;采用人宫颈癌SiHa和HeLa细胞体外模型,以顺铂为阳性对照品,采用MTT法测定2,3,4-三甲氧基查耳酮类衍生物对宫颈癌SiHa和HeLa细胞的增殖抑制活性;用流式细胞仪法测定对2种宫颈癌细胞增殖周期的影响和促凋亡作用。结果合成2,3,4-三甲氧基-4′甲氧基查耳酮(衍生物1),2,3,4-三甲氧基-2′,4′-二甲氧基查耳酮(衍生物2),2,3,4-三甲氧基-3′,4′-二甲氧基查耳酮(衍生物3)。当浓度为1~100μg/mL范围内,各衍生物对SiHa和HeLa细胞作用24、48、72 h时的增殖抑制率为6.6%~89.8%,抑制特征呈浓度和时间依赖型,抑制率高于先导化合物查耳酮B。其中衍生物3的活性最高,对SiHa和HeLa细胞的24 h凋亡率为15.0%~85.6%,可将HeLa细胞的增殖周期阻滞在G_2/M期。结论Lico B结构修饰后所得衍生物2,3,4-三甲氧基-3′,4′-二甲氧基查耳酮对宫颈癌SiHa和HeLa细胞有较强的抑制作用。

Objective To synthesize three chalcone derivatives by using licochalcone B as a lead compound;and to study anti-cervical cancer activity in vitro,effects of the proliferation cycle and the pro-apoptotic action on the cervical cancer cells.Methods The 2,3,4-trimethoxychalcones were synthesized by Claisen-Schmidt reaction using substituted acetophenone and substituted benzaldehyde.The human cervical cancer SiHa and HeLa cells were used as in vitro models,and cisplatin was used as positive control to determine the anti-cervical cancer activity of 2,3,4-trimethoxychalcone derivatives on SiHa and HeLa cells by MTT method;the effect of compounds on the proliferation cycle of cervical cancer cells and the pro-apoptotic effect were determined by flow cytometry.Results We successfully synthesized 2,3,4-trimethoxy-4′-methorxychalcone(Compound 1),2,3,4-trimethoxy-2′,4′-dimethoxychalcone(Compound2)and 2,3,4-trimethoxy-3′,4′-dimethoxychalcone(Compound 3).When the concentration was in the range of 1-100μg/mL,the inhibition rates of every compound on SiHa and HeLa cells at 24,48,72 h were at 6.6%-89.8%,with concentration-and time-dependent manners,which were higher than those of lead compound licochalcone B.The compound 3 was more active,the apoptotic rates for SiHa and HeLa cells were 15.0%-85.6%,and the cell cycle of HeLa cells was blocked in G\-2/M phase.Conclusion 2,3,4-trimethoxy-3′,4′-dimethoxychalcone,a derivative of Licochalcone B,possesses significant anti-cervical cancer activity on SiHa and HeLa cells.