Document Detail


10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones as highly active antimicrotubule agents: synthesis, antiproliferative activity, and inhibition of tubulin polymerization.
MedLine Citation:
PMID:  19220018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of 10-(2-oxo-2-phenylethylidene)-10H-anthracen-9-ones were synthesized and evaluated for interactions with tubulin and for antiproliferative activity against a panel of human and rodent tumor cell lines. The 4-methoxy analogue 17b was most potent, displaying IC(50) values ranging from 40 to 80 nM, including multidrug resistant phenotypes, and had excellent activity as an inhibitor of tubulin polymerization (IC(50) = 0.52 microM). Concentration-dependent flow cytometric studies showed that KB/HeLa cells treated with 17b were arrested in the G2/M phases of the cell cycle (EC(50) = 90 nM). In competition experiments, 17b strongly displaced [(3)H]-colchicine from its binding site in the tubulin. The results obtained demonstrate that the antiproliferative activity is related to the inhibition of tubulin polymerization.
Authors:
Helge Prinz; Peter Schmidt; Konrad J B?hm; Silke Baasner; Klaus M?ller; Eberhard Unger; Matthias Gerlach; Eckhard G G?nther
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  52     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2010-06-03     Completed Date:  2010-06-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1284-94     Citation Subset:  IM    
Affiliation:
Institute of Pharmaceutical and Medicinal Chemistry, Westphalian Wilhelms-University, Munster, Germany. prinzh@uni-muenster.de
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MeSH Terms
Descriptor/Qualifier:
Anthracenes / chemical synthesis*,  chemistry,  pharmacology
Binding, Competitive
Cell Line, Tumor
Cell Proliferation / drug effects
Colchicine / metabolism
Drug Resistance, Multiple
Drug Resistance, Neoplasm
Drug Screening Assays, Antitumor
G2 Phase / drug effects
Humans
Protein Binding
Structure-Activity Relationship
Tubulin / metabolism
Tubulin Modulators / chemical synthesis*,  chemistry,  pharmacology
Chemical
Reg. No./Substance:
0/10-(2-(4-methoxyphenyl)-2-oxoethylidene)-10H-anthracen-9-one; 0/Anthracenes; 0/Tubulin; 0/Tubulin Modulators; 64-86-8/Colchicine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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