| The design, synthesis, and anti-tumor mechanism study of N-phosphoryl amino acid modified resveratrol analogues. | |
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MedLine Citation:
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PMID: 18952444 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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A novel series of trans-N-phosphoryl amino acid modified resveratrol analogues were synthesized and evaluated in vitro for their cytotoxic effects against CNE-1 and CNE-2 cell lines. These analogues showed good anti-proliferative activity, among which 8d, 8e, 8j, and 9d displayed much stronger inhibition effect than resveratrol and 8d showed the most potent activity with IC(50) value at 3.45+/-0.82microM. The anti-tumor effects of 8d, 8e, 8j, and 9d were due to the induction of apoptosis, confirmed by the DNA fragmentation and flow cytometry analysis using PI (propidium iodide) staining and Annexin-V-FITC/PI staining assay. The PI staining assay also showed that 8d, 8e, 8j, and 9d caused cell cycles arrest at G(0)-G(1) phase which finally led to cell apoptosis. Further mechanism study on compound 8d against CNE-2 cells has shown the PARP cleavage, which is a hallmark of caspase-3 activation, as well as the activation of caspase-9, and the intracellular ROS generation. These results all suggest that 8d induced a mitochondrial-dependent apoptosis pathway. |
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Authors:
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Huachen Liu; Aijun Dong; Chunmei Gao; Chunyan Tan; Hongxia Liu; Xuyu Zu; Yuyang Jiang |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-10-12 |
Journal Detail:
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Title: Bioorganic & medicinal chemistry Volume: 16 ISSN: 1464-3391 ISO Abbreviation: Bioorg. Med. Chem. Publication Date: 2008 Dec |
Date Detail:
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Created Date: 2008-11-17 Completed Date: 2009-01-09 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9413298 Medline TA: Bioorg Med Chem Country: England |
Other Details:
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Languages: eng Pagination: 10013-21 Citation Subset: IM |
Affiliation:
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Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing 100084, China. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents, Phytogenic
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chemical synthesis*,
chemistry,
pharmacology* Apoptosis Caspases / metabolism DNA Fragmentation Hela Cells Humans Inhibitory Concentration 50 K562 Cells Mitochondria / drug effects, metabolism Mitochondrial Membranes / drug effects, metabolism Phosphoamino Acids / chemistry* Stilbenes / chemical synthesis, chemistry*, pharmacology Structure-Activity Relationship Tumor Cells, Cultured |
| Chemical | |
Reg. No./Substance:
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0/Antineoplastic Agents, Phytogenic; 0/Phosphoamino Acids; 0/Stilbenes; 501-36-0/resveratrol; EC 3.4.22.-/Caspases |
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