Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 24, Issue 6, Pages 1511-1518Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2014.02.001
Keywords
Dehydroabietic acid; Dipeptide; Cytotoxicity; Apoptosis
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Funding
- 973 project [2011CB512005, 2012CB723501]
- National Natural Science Foundation of China [81260472, 21362002]
- Guangxi Natural Science Foundation of China [2011GXNSFD018010, 2010GXNSFF013001]
- Guilin Scientific Research and Technological Development Project [20110106-2, 20120108-6]
- Bagui Scholar project
- Foundation of Ministry of Education Innovation Team [IRT1225]
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A series of dipeptide derivatives from dehydroabietic acid were designed and synthesized as novel antitumor agents. The antitumor activities screening indicated that many compounds showed moderate to high levels of inhibition activities against NCI-H460, HepG2, SK-OV-3, BEL-7404, HeLa and HCT-116 cancer cell lines and that some displayed more potent inhibitory activities than commercial anticancer drug 5-fluorouracil. The mechanism of representative compound 7b was studied by AO/EB staining, Hoechst 33258 staining, JC-1 mitochondrial membrane potential staining, TUNEL assay, DNA ladder assay and flow cytometry, which exhibited that the compound could induce apoptosis in HeLa cells. Further investigation showed that compound 7b induced apoptosis of HeLa cells through a mitochondrial pathway. (C) 2014 Elsevier Ltd. All rights reserved.
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