摘要
目的对18β-甘草次酸2位、3位、11位和29位进行结构修饰,增强其抑制白血病细胞生长和诱导细胞凋亡活性。方法以18β-甘草次酸为起始原料,经氧化、酯化、缩合、脱氢等反应得到目标化合物;以台盼蓝排斥试验和AO-EB双荧光染色法检测目标化合物对HL-60细胞的生长抑制活性及诱导细胞凋亡活性。结果与结论合成了14个18β-甘草次酸类化合物,其结构经核磁共振氢谱、红外光谱及质谱确证。体外活性测定结果表明,合成的化合物表现出不同程度的细胞生长抑制活性,其中A环结构改造后的化合物Ⅶ和Ⅸ活性较强,且呈现时间和剂量依赖性。
Aim To modify 18β-glycyrrhetinic acid structure for increasing its antileukemia activity.Methods Target compounds were obtained by oxidation,esterification,condensation and dehydrogenation from 18β-glycyrrhetinic acid as starting material.Cell growth inhibitory effect was measured by directly counting cell numbers after treatment with these compounds.Apoptosis cells were evaluated morphologically after staining with acridine orange and ethidium bromide in HL-60 cells.Results and conclusion Fourteen derivatives of 18β-glycyrrhetinic acid were synthesized and their structures were characterized according to the spectra of MS,IR and 1H-NMR.Some derivatives exhibited cell growth inhibitory in vitro test.Among them,compounds Ⅶ and Ⅸ exhibited the most potent for cell growth inhibitory and apoptosis induction in time and dose dependent manners.
出处
《中国药物化学杂志》
CAS
CSCD
2010年第2期84-89,共6页
Chinese Journal of Medicinal Chemistry
基金
国家科技部国际科技合作项目(2009DFA31200)
辽宁省科学技术计划项目(2008226023)
