齐墩果酸衍生物的合成及抗肿瘤活性研究
Synthesis of oleanolic acid derivatives and their antitumor activity
杜新春 1宋艳玲 2何鑫1
作者信息
- 1. 沈阳科技学院化学与化工系 沈阳 110170
- 2. 沈阳化工大学制药与生物工程学院 沈阳 110142
- 折叠
摘要
目的:以齐墩果酸为先导化合物,设计并合成一系列基于MEK激酶靶点的齐墩果酸衍生物.方法:利用计算机辅助药物设计技术,确定能和关键位点结合的活性基团.以齐墩果酸为起始原料,经过C-28 位酯化、C-3 位引入酰胺基得到目标产物.结果:合成了 4 个新型齐墩果酸衍生物Ⅰ 1～Ⅰ 4,其结构经MS、1H-NMR、13C-NMR确证,体外研究显示它们的抗肿瘤活性显著高于母体齐墩果酸,其中Ⅰ 4 对HepG2 细胞显示出较强的抑制活性(IC50 值为19.12 μmol/L).结论:Ⅰ 4 有成为新型MEK抑制剂的潜力.
Abstract
Objective:To design and synthesize a series of oleanolic acid derivatives based on MEK kinase target using oleanolic acid as the lead compound.Methods:Computer-aided drug design technology was used to determine the active groups that can bind to key sites.Oleanolic acid was used as starting material,the target compounds were obtained by esterification at position C-28 and introduction of an amide group at position C-3.Results:Four oleanolic acid derivativeⅠ1-Ⅰ4 were synthesized and their structures were identified by MS,1H-NMR and 13C-NMR,and their antitumor activity in vitro was significantly higher than that of maternal oleanolic acid,in which compoundsⅠ4 showed strong inhibitory activity against HepG 2 cells(IC50=19.12 mmol/L).Conclusion:CompoundⅠ4 has the potential to be a novel MEK inhibitor.
关键词
齐墩果酸衍生物/合成/抗肿瘤活性/计算机辅助药物设计Key words
oleanolic acid derivatives/synthesis/antitumor activity/computer aided-drug design引用本文复制引用
出版年
2024
NETL
NSTL
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