Abstract |
A series of acyclic enediynes showing significant inhibition on the growth of tumor cancer is disclosed. To investigate the structure-activity relationship, compounds 12-33 were synthesized. Among them, compound 17 showed most potent growth inhibition activity against all tumor cell lines at low concentration, such as SR (0.4microM) and MDA-MB-435 (0.8microM), and almost completely blocked cell cycle in G2/M phase via controlling Cyclin A and Cdc25C expression. On the other hand, compound 29 showed potent induced apoptosis activity by inducing activation of caspase-3, -8, and -9. Thus, this article disclosed a new multiple- protein regulator in cell cycle regulation and induced apoptosis to achieve the goal of anticancer drug.
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Authors | Yu-Hsiang Lo, I-Ling Lin, Chi-Fong Lin, Cheng-Chung Hsu, Sheng-Huei Yang, Shinne-Ren Lin, Ming-Jung Wu |
Journal | Bioorganic & medicinal chemistry
(Bioorg Med Chem)
Vol. 15
Issue 13
Pg. 4528-36
(Jul 01 2007)
ISSN: 0968-0896 [Print] England |
PMID | 17485212
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antineoplastic Agents
- Caspase Inhibitors
- Cell Cycle Proteins
- Cyclin A
- Indicators and Reagents
- CDC25C protein, human
- cdc25 Phosphatases
- Caspases
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Topics |
- Antineoplastic Agents
(chemical synthesis, pharmacology)
- Apoptosis
(drug effects)
- Blotting, Western
- Caspase Inhibitors
- Caspases
(metabolism)
- Cell Cycle
(drug effects)
- Cell Cycle Proteins
(antagonists & inhibitors, biosynthesis)
- Cell Line, Tumor
- Cell Proliferation
(drug effects)
- Cyclin A
(antagonists & inhibitors, biosynthesis)
- Humans
- Indicators and Reagents
- Quantitative Structure-Activity Relationship
- Signal Transduction
(drug effects)
- Structure-Activity Relationship
- cdc25 Phosphatases
(antagonists & inhibitors, biosynthesis)
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