Source:http://linkedlifedata.com/resource/pubmed/id/21080725
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
24
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| pubmed:dateCreated |
2010-12-17
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| pubmed:abstractText |
The synthesis and antiproliferative activity of a new series of rigid analogues of combretastatin A-4 are described which contain the 1,4-diaryl-2-azetidinone (?-lactam) ring system in place of the usual ethylene bridge present in the natural combretastatin stilbene products. These novel compounds are also substituted at position 3 of the ?-lactam ring with an aryl ring. A number of analogues showed potent nanomolar activity in human MCF-7 and MDA-MB-231 breast cancer cell lines, displayed in vitro inhibition of tubulin polymerization, and did not cause significant cytotoxicity in normal murine breast epithelial cells. 4-(4-Methoxyaryl)-substituted compound 32, 4-(3-hydroxy-4-methoxyaryl)-substituted compounds 35 and 41, and the 3-(4-aminoaryl)-substituted compounds 46 and 47 displayed the most potent antiproliferative activity of the series. ?-Lactam 41 in particular showed subnanomolar activity in MCF-7 breast cancer cells (IC??= 0.8 nM) together with significant in vitro inhibition of tubulin polymerization and has been selected for further biochemical assessment. These novel ?-lactam compounds are identified as potentially useful scaffolds for the further development of antitumor agents that target tubulin.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Azetidines,
http://linkedlifedata.com/resource/pubmed/chemical/Stilbenes,
http://linkedlifedata.com/resource/pubmed/chemical/Tubulin,
http://linkedlifedata.com/resource/pubmed/chemical/Tubulin Modulators,
http://linkedlifedata.com/resource/pubmed/chemical/combretastatin A-4
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
|
| pubmed:issn |
1520-4804
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| pubmed:author | |
| pubmed:issnType |
Electronic
|
| pubmed:day |
23
|
| pubmed:volume |
53
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
8569-84
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| pubmed:meshHeading |
pubmed-meshheading:21080725-Animals,
pubmed-meshheading:21080725-Azetidines,
pubmed-meshheading:21080725-Cattle,
pubmed-meshheading:21080725-Cell Line, Tumor,
pubmed-meshheading:21080725-Crystallography, X-Ray,
pubmed-meshheading:21080725-Drug Screening Assays, Antitumor,
pubmed-meshheading:21080725-Epithelial Cells,
pubmed-meshheading:21080725-Female,
pubmed-meshheading:21080725-Humans,
pubmed-meshheading:21080725-Mammary Glands, Animal,
pubmed-meshheading:21080725-Models, Molecular,
pubmed-meshheading:21080725-Molecular Structure,
pubmed-meshheading:21080725-Protein Binding,
pubmed-meshheading:21080725-Stereoisomerism,
pubmed-meshheading:21080725-Stilbenes,
pubmed-meshheading:21080725-Structure-Activity Relationship,
pubmed-meshheading:21080725-Tubulin,
pubmed-meshheading:21080725-Tubulin Modulators
|
| pubmed:year |
2010
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| pubmed:articleTitle |
Synthesis and evaluation of azetidinone analogues of combretastatin A-4 as tubulin targeting agents.
|
| pubmed:affiliation |
School of Pharmacy and Pharmaceutical Sciences, Centre for Synthesis and Chemical Biology, Trinity College Dublin, Dublin 2, Ireland.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|