Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro

doi:10.6023/cjoc201803043

Chin. J. Org. Chem. ›› 2018, Vol. 38 ›› Issue (10): 2633-2638.DOI: 10.6023/cjoc201803043 Previous Articles Next Articles

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一种新颖的含呋喃酮骨架苦参碱衍生物合成及体外抗癌活性初步评价

马富莉, 张姣, 李明, 于家瀛, 罗薇, 李学强, 魏梦雪

宁夏大学化学化工学院省部共建煤炭高效利用与绿色化工国家重点实验室银川 750021

收稿日期:2018-03-26 修回日期:2018-05-25 发布日期:2018-06-22
通讯作者: 李学强,E-mail:lixq@nxu.edu.cn;魏梦雪,E-mail:weimengxue@nxu.edu.cn E-mail:lixq@nxu.edu.cn;weimengxue@nxu.edu.cn
基金资助:
国家自然科学基金（No.21462032）、宁夏自然科学基金（No.NZ17001）、宁夏回族自治区国内一流学科建设（No.NXYLXK2017A04）、中国西部一流大学重大创新（No.ZKZD2017003）、宁夏大学研究生创新（No.GIP2018048）和宁夏大学大学生创新创业训练计划（No.Q201710749028）资助项目.

Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro

Ma Fuli, Zhang Jiao, Li Ming, Yu Jiaying, Luo Wei, Li Xueqiang, Wei Mengxue

State Key Laboratory of High-efficiency Utilization of Coal and Green Chemical Engineering, School of Chemistry and Chemical Engineering, Ningxia University, Yinchuan 750021

Received:2018-03-26 Revised:2018-05-25 Published:2018-06-22
Contact: 10.6023/cjoc201803043 E-mail:lixq@nxu.edu.cn;weimengxue@nxu.edu.cn
Supported by:
Project supported by the National Natural Science Foundation of China (No. 21462032), the Natural Science Foundation of Ningxia Hui Antonomous Region (No. NZ17001), the Discipline Project of Ningxia Hui Antonomous Region (No. NXYLXK2017A04), the Major Innovation Projects for Building First-class Universities in China's Western Region (No. ZKZD2017003), the Graduate Innovation of Ningxia University (No. GIP2018048) and the College Students' Innovative and Entrepreneurship Training Program of Ningxia University (No. Q201710749028).

1. Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro.PDF(1531KB)

Abstract

Sophora acid sodium was synthesized from matrine, where the lactam unit was saponificated in the presence of aqueous sodium hydroxide. Then, esterfication of the sodium salt with methanol and ethanol produced the corresponding esters in 60%～83% yields. Subsequently, the two pharmacophores, matrine esters and 5-alkoxy-3,4-dibromo-2 (5H)-furan ketones were combined through a C—N coupling reaction, producing a series of novel matrine derivatives with good yields. The anti-tumor activities of the matrine derivatives against human hepatoma SMMC-7721 cell lines were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The test results showed that the matrine derivatives can effectly inhibit proliferation of liver cancer cells, and the compound methyl 3-(2-((S)-4-bromo-2-(((1S,2R,5S)-2-isopropyl-5-methylcyclohexyl)oxy)-5-oxo-2,5-dihydrofuran-3-yl)dodecahydropyrido[3,2,1-ij][1,6]naphthyridin-1- yl)propanoate (5a) possessed stronger inhibitory activity against SMMC-7721 cell lines with the IC₅₀ value of 0.0004 μmol/L at 24 h, showing markedly higher inhibitory activity in vitro than cytosine arabinoside (0.4578 μmol/L), vincristine (0.1284 μmol/L) and the parent compound matrine (0.9018 μmol/L).

Key words: sophora acid ester, 5-alkoxy-3,4-dibromo-2(5H)-furan ketone, anti-tumor activity

Cite this article

Ma Fuli, Zhang Jiao, Li Ming, Yu Jiaying, Luo Wei, Li Xueqiang, Wei Mengxue. Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro[J]. Chin. J. Org. Chem., 2018, 38(10): 2633-2638.

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一种新颖的含呋喃酮骨架苦参碱衍生物合成及体外抗癌活性初步评价

Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro

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