A Series of New Ligustrazine-Triterpenes Derivatives as Anti-Tumor Agents: Design, Synthesis, and Biological Evaluation

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 conjun...

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Bibliographic Details
Published in:International journal of molecular sciences 2015-09, Vol.16 (9), p.21035-21055
Main Authors: Xu, Bing, Chu, Fuhao, Zhang, Yuzhong, Wang, Xiaobo, Li, Qiang, Liu, Wei, Xu, Xin, Xing, Yanyi, Chen, Jing, Wang, Penglong, Lei, Haimin
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemical synthesis
Antineoplastic Agents - chemistry
Antineoplastic Agents - pharmacology
Apoptosis
Biosynthesis
Calcium - metabolism
Cancer therapies
Cell Line, Tumor
Cell Proliferation - drug effects
Cell Survival - drug effects
Cisplatin - pharmacology
combination principles
Cytotoxicity
cytotoxicity selectivity
Dogs
HeLa Cells
Hep G2 Cells
HT29 Cells
Humans
ligustrazine-triterpenes derivatives
Madin Darby Canine Kidney Cells
MCF-7 Cells
Membrane Potential, Mitochondrial - drug effects
Pyrazines - chemical synthesis
Pyrazines - chemistry
Pyrazines - pharmacology
Structure-Activity Relationship
Triterpenes - chemical synthesis
Triterpenes - chemistry
Triterpenes - pharmacology
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Summary: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 (IC5020 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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms160921035