Design, Synthesis, and Biological Evaluation of Novel Nitrogen Heterocycle-Containing Ursolic Acid Analogs as Antitumor Agents

被引：26

作者：

Wang, Wenzhi ^{[1
]}

Lei, Lei ^{[1
]}

Liu, Zhi ^{[1
]}

Wang, Hongbo ^{[1
]}

Meng, Qingguo ^{[1
]}

机构：

[1] Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & B, Key Lab Mol Pharmacol & Drug Evaluat, Sch Pharm,Minist Educ, Yantai 264005, Peoples R China

来源：

MOLECULES | 2019年 / 24卷 / 05期

基金：

中国国家自然科学基金;

关键词：

ursolic acid analogues; synthesis; nitrogen heterocycles; apoptosis; antitumor activity; IN-VITRO; DERIVATIVES; CELLS; RESISTANCE;

D O I：

10.3390/molecules24050877

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nineteen ursolic acid analogues were designed, synthesized, and evaluated for their antiproliferative activity against the Hela and MKN45 cell lines. Some compounds containing a piperazine moiety displayed moderate to high levels of antitumor activities against the tested cancer cell lines. The most potent compound shares the IC50 value of 2.1 mu M and 2.6 mu M for the Hela and MKN45 cell lines, respectively. Further mechanism studies and in vivo antitumor studies have shown that it decreased the apoptosis regulator (BCL2/BAX) ratio, disrupted mitochondrial potential and induced apoptosis, and suppressed the growth of Hela xenografts in nude mice.

引用

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