摘要
目的以异甘草素（ILG）为先导化合物进行化学合成其衍生物3-甲氧基异甘草素（3-MO-ILG）,探讨其体外抗宫颈癌活性。方法采用硼酸催化高温法、羟基保护法、微波辅助碱催化法3种方法进行羟醛缩合反应而制备目标化合物;以人宫颈癌Si Ha细胞为体外模型,用3-（4,5-二甲基噻唑-2）-2,5-二苯基四氮唑溴盐（MTT）法测定对癌细胞增长的抑制率;用流式细胞仪测定促进癌细胞凋亡作用,以顺铂作为阳性对照组。结果用硼酸催化高温法、羟基保护法、微波辅助碱催化法3种方法所得到的3-甲氧基异甘草素产率分别为8.9%、9.27%和57.60%。3-甲氧基异甘草素对Si Ha细胞具有较强抑制增殖作用,当药物浓度为20～150μg/mL、作用时间为24 h时,其抑制率可达93.5%;当作用时间达到72 h时,抑制率最强。3-甲氧基异甘草素在100μg/mL时,对Si Ha细胞早期凋亡率为38.6%,晚期凋亡率为1.4%,具有明显的促细胞凋亡作用。结论微波辅助碱催化方法在查尔酮类化合物的合成中具有产率较高的方法。3-甲氧基异甘草素对Si Ha细胞具有较强抑制增殖作用,并且具有明显浓度和时间依赖性;同时对Si Ha细胞具有明显的促细胞凋亡作用。
Objective Taking isoliquiritigenin as the lead compounds to synthesize 3-Methoxy isoliquiritigenin,which is the derivatives of isoliquiritigenin,and explore its anticancer activity to human cervical cancer cell in vitro. Methods The target compound was prepared by aldol condesation reaction with three methods（ catalyzed method on high temperature by boric acid,hydroxyl protected method,microwave-assisted base-catalyzed method）. Taking human cervical cancer Si Ha as the vitro model,the inhibition rate of Si Ha cell was detected by MTT method and the apoptosis of Si Ha cell was measured by flow cytometry. Cisplatin was positive control group. Results The yield of the target product was 8. 9%,9. 27% and 57. 60% respectively by using above three methods. 3-methoxy isoliquiritigenin had a stronger inhibitory effect on Si Ha cells. When the drug concentration of 3-MO-ILG was 20-150 μg / mL,and the action time was 24 h,the inhibition rate was 93. 5%. When the drug concentration of3-MO-ILG was 100 μg / mL,it had the clear pro-apoptotic effect on Siha cells（ the rate of early period apoptotic was38. 6%,and the rate of late apoptotic was 1. 4%）. Conclusion Microwave-assisted base-catalyzed method has higher yield on synthesis of chalcones. 3-methoxy isoliquiritigenin had a stronger inhibitory effect and pro-apoptotic effect on Si Ha cells and had significant concentration and time dependence.
出处
《新疆医科大学学报》
CAS
2016年第2期173-178,共6页
Journal of Xinjiang Medical University
基金
国家自然科学基金(81260379)
新疆研究生科研创新项目(XJGRI2014094)
关键词
3-甲氧基异甘草素
羟醛缩合反应
人宫颈癌Si
Ha细胞
抗癌活性
3-Methoxy isoliquiritigenin
aldol condesation reaction
the Si Ha cell of human cervircal cancer
antitumor activity
