佟思淼　孟艳秋

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Claisen Schmidt 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。

关  键  词：熊果酸;结构改造;抗肿瘤活性;分子对接

中图分类号：R914.5       文献标识码： A       文章编号： 1671-0460（2020）07-1261-05

Structural Modification and in vitro Antitumor

Activity of Ursolic Acid Analogues

TONG Si-miao， MENG Yan-qiu

（Shenyang University of Chemical Technology， Shenyang Liaoning 110142， China）

Abstract： 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 and Ⅱ4 showed stronger antitumor activity. The structurally modified ursolic acid derivatives have certain antitumor activity and are worthy of further study.

Key words： Ursolic acid; Derivatives; Antitumor activity; Molecular docking

熊果酸是从天然植物中提取出的一种五环三萜类的化合物，具有抗艾滋病[1]、抗白血病[2]、抗糖尿病[3]、抗癌等多种生物学效应，属于乌苏烷型五环三萜类化合物，具备五环三萜的典型结构及药理活性。但熊果酸对癌细胞的细胞毒性较强，不仅仅能够诱导癌细胞十七进入凋亡期，更能够抑制癌细胞的增值。熊果酸并未成为抗肿瘤的明星药物，主要原因是因为其在生物体中的利用程度较低，使得熊果酸的临床应用和市场发展遭受很大阻碍。为了更有效地解决这些问题，本文通过分子对接，设计并合成了12个化合物，并测得体外抗肿瘤活

性[4-9]。

随着医学的发展，越来越多的研究者重视细胞内的发展，也有越来越多的科学家开始利用细胞分离增殖。……