Novel acyclic enediynes inhibit Cyclin A and Cdc25C expression and induce apoptosis phenomenon to show potent antitumor proliferation.

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.

• 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)

Chemical References

• Antineoplastic Agents
• Caspase Inhibitors
• Cell Cycle Proteins
• Cyclin A
• Indicators and Reagents
• CDC25C protein, human
• cdc25 Phosphatases
• Caspases

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)