title: A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation.
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.
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. weichenxubing@126.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Xu
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. chufhao@163.com.
authors.forename: Fuhao
authors.initials: F
authors.lastname: Chu
authors.affiliation: Department of Pathology, Beijing University of Chinese Medicine, Beijing 100102, China. zyz100102@126.com.
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center of Scientific Experiment, Beijing University of Chinese Medicine, Beijing 100102, China. xiaobo1001@gmail.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. lq_cn@126.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Management, Beijing University of Chinese Medicine, Beijing 100102, China. nolanlucky@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. xu.xin@vip.126.com.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. xingyanyi1988@126.com.
authors.forename: Yanyi
authors.initials: Y
authors.lastname: Xing
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. cjttmc@sina.cn.
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. wpl581@126.com.
authors.forename: Penglong
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Chinese Pharmacy, Beijing University of Chinese Medicine, Beijing 100102, China. hm_lei@126.com.
authors.forename: Haimin
authors.initials: H
authors.lastname: Lei
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004285:Dogs; D019073:HT29 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D061985:Madin Darby Canine Kidney Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D011719:Pyrazines; D014315:Triterpenes; D002945:Cisplatin; D002118:Calcium; C017953:tetramethylpyrazine
keywords: apoptosis; combination principles; cytotoxicity selectivity; ligustrazine-triterpenes derivatives