摘要
以熊果酸为先导化合物,设计并合成其衍生物并检测体外抗肿瘤活性。利用熊果酸与各种芳香醛的缩合反应,采用计算机辅助设计,对设计的化合物进行筛选;合成分子对接分最高的的12个化合物。对其C-2位ClaisenSchmidt缩合反应,C-3位以及C-28位羧基进行结构改造;采用MTT法测试目标化合物对人肝癌细胞(HepG2)和人肺癌细胞(A549)的体外抗肿瘤活性。目标化合物对这两种细胞株的抑制活性均优于母体熊果酸,其中化合物Ⅰ6和Ⅱ4表现出较强的抗肿瘤活性。经结构改造后的熊果酸衍生物具有一定的抗肿瘤活性,值得进一步研究。
Ursolic acid was used as the lead compound,its derivatives were designed and synthesized,and its in vitro antitumor activity was tested.In this paper,the condensation reaction between ursolic acid and various aromatic aldehydes was used to screen the designed compounds by computational aided design.The 12 compounds with the highest molecular score were synthesized.The C-2 Claisen Schmidt condensation reaction,C-3 and C-28 carboxyl groups were modified;The anti-tumor activity of the target compound against human liver cancer cells(HepG2)and human lung cancer cells(A549)in vitro was measured by MTT assay.Inhibitory activity of the target compounds against the two kinds of cell lines was superior to the parent ursolic acid,compoundⅠ6 andⅡ4 showed stronger antitumor activity.The structurally modified ursolic acid derivatives have certain antitumor activity and are worthy of further study.
作者
佟思淼
孟艳秋
TONG Si-miao;MENG Yan-qiu(Shenyang University of Chemical Technology,Shenyang Liaoning 110142,China)
出处
《当代化工》
CAS
2020年第7期1261-1264,1268,共5页
Contemporary Chemical Industry
基金
国家自然科学基金(项目编号:21372156)
辽宁省创新团队资助立项(项目编号:LT2017009)
辽宁省教育厅科研项目(项目编号:LFD2017004)
辽宁省重点研发计划项目(项目编号:2019JH2/10300034)
关键词
熊果酸
结构改造
抗肿瘤活性
分子对接
Ursolic acid
Derivatives
Antitumor activity
Molecular docking
