Synthesis of Oleanolic Acid-Dithiocarbamate Conjugates and Evaluation of Their Broad-Spectrum Antitumor Activities

被引:3
作者
Tang, Liyao [1 ]
Zhang, Yan [1 ]
Xu, Jinrun [1 ]
Yang, Qingfan [2 ]
Du, Fukuan [1 ,3 ]
Wu, Xu [1 ,3 ]
Li, Mingxing [1 ,3 ]
Shen, Jing [1 ,3 ]
Deng, Shuai [1 ,3 ]
Zhao, Yueshui [1 ,3 ]
Xiao, Zhangang [2 ,3 ]
Chen, Yu [1 ,3 ]
机构
[1] Southwest Med Univ, Sch Pharm, Dept Pharmacol, Lab Mol Pharmacol, Luzhou 646000, Peoples R China
[2] Southwest Med Univ, Affiliated Hosp, Dept Oncol, Luzhou 646000, Peoples R China
[3] Southwest Med Univ, Cell Therapy & Cell Drugs Luzhou Key Lab, Luzhou 646000, Peoples R China
来源
MOLECULES | 2023年 / 28卷 / 03期
基金
中国国家自然科学基金;
关键词
structural modification; oleanolic acid; natural product derivative; dithiocarbamate; hybrid strategy; antitumor activity; DESIGN; DERIVATIVES; INHIBITORS; HYBRIDS;
D O I
10.3390/molecules28031414
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
Efficient and mild synthetic routes for bioactive natural product derivatives are of current interest for drug discovery. Herein, on the basis of the pharmacophore hybrid strategy, we report a two-step protocol to obtain a series of structurally novel oleanolic acid (OA)-dithiocarbamate conjugates in mild conditions with high yields. Moreover, biological evaluations indicated that representative compound 3e exhibited the most potent and broad-spectrum antiproliferative effects against Panc1, A549, Hep3B, Huh-7, HT-29, and Hela cells with low cytotoxicity on normal cells. In terms of the IC50 values, these OA-dithiocarbamate conjugates were up to 30-fold more potent than the natural product OA. These compounds may be promising hit compounds for the development of novel anti-cancer drugs.
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页数:18
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