Citation: 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]. Chinese Journal of Organic Chemistry, ;2018, 38(10): 2633-2638. doi: 10.6023/cjoc201803043 shu

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

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

Corresponding author: Li Xueqiang, lixq@nxu.edu.cn Wei Mengxue, weimengxue@nxu.edu.cn

^†

Received Date: 26 March 2018
Revised Date: 25 May 2018
Available Online: 22 October 2018
Fund Project: the Major Innovation Projects for Building First-class Universities in China's Western Region ZKZD2017003the Discipline Project of Ningxia Hui Antonomous Region NXYLXK2017A04the Graduate Innovation of Ningxia University GIP2018048the College Students' Innovative and Entrepreneurship Training Program of Ningxia University Q201710749028the National Natural Science Foundation of China 21462032Project 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)the Natural Science Foundation of Ningxia Hui Antonomous Region NZ17001

Figures(3)

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