A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design,Synthesis, and Biological Evaluation |
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| Authors: | Bing Xu Fuhao Chu Yuzhong Zhang Xiaobo Wang Qiang Li Wei Liu Xin Xu Yanyi Xing Jing Chen Penglong Wang Haimin Lei |
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| Affiliation: | 1.School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China; E-Mails: (B.X.); (F.C.); (Q.L.); (X.X.); (Y.X.); (J.C.);2.Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China; E-Mail: ;3.Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing 100102, China; E-Mail: ;4.School of Management, Beijing University of Chinese Medicine, Beijing 100102, China; E-Mail: |
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| Abstract: | A series of novel ligustrazine-triterpenes derivatives was designed, synthesized and screened for their cytotoxicity against five cancer cell lines (Bel-7402, HepG2, HT-29, Hela, and MCF-7) and Madin-Darby canine kidney (MDCK). Current study suggested that most of the ligustrazine-triterpenes conjunctions showed better cytotoxicity than the starting materials. In particular, compound 4a exhibited better cytotoxic activity (IC50 < 5.23 μM) against Bel-7402, HT-29, MCF-7, Hela, and HepG2 than the standard anticancer drug cisplatin (DDP). The cytotoxicity selectivity detection revealed that 4a exhibited low cytotoxicity (IC50 > 20 μM) towards MDCK cells. A combination of fluorescence staining observation and flow cytometric analysis indicated that 4a could induce HepG2 cell apoptosis. Further studies suggested that 4a-induced apoptosis is mediated through depolarization of the mitochondrial membrane potential and increase of intracellular free Ca2+ concentration. In addition, the structure-activity relationships of these derivatives were briefly discussed. |
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| Keywords: | ligustrazine-triterpenes derivatives cytotoxicity selectivity combination principles apoptosis |
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