熊果酸衍生物的合成及抗肿瘤活性的研究  

Study on the Synthesis and Antitumor Activity of Ursolic Acid Derivatives

作　　者：丁明雪 孟艳秋 DING Ming-xue;MENG Yan-qiu(Shenyang University of Chemical Technology,Shenyang 110142,China)

机构地区：[1]沈阳化工大学制药与生物工程学院,辽宁沈阳110142

出　　处：《沈阳化工大学学报》2022年第2期123-127,共5页Journal of Shenyang University of Chemical Technology

基　　金：国家自然科学基金(21372156);辽宁省创新团队资助立项(LT2017009);辽宁省教育厅科研项目(LFD2017004);辽宁省教育厅科学研究项目(LJ2020025);辽宁省重点研发计划项目(2019JH2/10300034);沈阳市重大科技成果转化项目(20-203-5-45);沈阳化工大学重点攻关项目(LDB2019001)。

摘　　要：熊果酸是天然抗癌药物之一,研究发现其能够抑制肿瘤细胞的很多阶段.为提高其生物活性,以熊果酸为先导化合物,在其A环上首先将C-3位羟基氧化成为一个羰基,最终形成肟基并与氯乙酰氯反应,同时对C-28位羧基进行酯化结构修饰,设计合成了5个新型熊果酸衍生物,其结构经^(1)H-NMR、MS等确认.采用MTT法,选用3种癌细胞系(HeLa、SKOV3和BGC-823)对所得化合物进行初步的体外抗肿瘤活性测试,结果表明:所测化合物对HeLa、SKOV3和BGC-823肿瘤细胞的抑制作用均强于母体熊果酸,其中化合物Ⅰ_(4)表现出较为显著的抗肿瘤活性,具有比阳性对照药物吉非替尼更高的抗肿瘤活性,值得进一步研究.Ursolic acid is one of the natural anticancer drugs, which has been found to inhibit many stages of tumor cells.In order to improve its biological activity with ursolic acid as the lead compound, the hydroxyl group at position C-3 was oxidized into a carbonyl group on its A ring, and finally formed an oxime and reacted group with chloroacetyl chloride.Meanwhile, the C-28 carboxyl group was modified by esterification structure, and five new ursolic acid derivatives were designed and synthesized.Their structures were confirmed by ^(1)H-NMR and MS,etc.Three cancer cells(SKOV3 and HeLa, BGC-823)were selected by MTT method to test the antitumor activity of the obtaind compounds in vitro.The results show that the inhibitory effect of the measured compounds on HeLa, SKOV3 and BGC-823 cancer cell inhibitory effect is stronger than that of the maternal ursolic acid, which compound Ⅰ_(4) showed more significant antitumor activity and higher antitumor activity than the positive control drug gefitinib, which is worthy of further study.

关 键 词：熊果酸 结构修饰 抗肿瘤活性 

分 类 号：R914[医药卫生—药物化学]