Chinese Journal of Organic Chemistry >
Synthesis of Novel Matrine Derivatives Containing Furanone Skeleton and Preliminary Evaluation of Their Anticancer Activity in Vitro
Received date: 2018-03-26
Revised date: 2018-05-25
Online published: 2018-06-22
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).
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).
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
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