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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2011-9-15
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pubmed:abstractText |
Potential binding modes of (+)-discodermolide at the paclitaxel binding site of tubulin have been identified by computational studies based on earlier structural and SAR data. Examination of the prospective binding modes reveal that the aromatic pocket occupied by the paclitaxel side chain is unoccupied by (+)-discodermolide. Based on these findings, a small library of (+)-discodermolide-paclitaxel hybrids have been designed and synthesized. Biological evaluation reveals a two- to eight-fold increase in antiproliferative activity compared to the parent molecule using the A549 and MCF-7 cancer cell lines.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1520-4804
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
22
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pubmed:volume |
54
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6319-27
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pubmed:meshHeading |
pubmed-meshheading:21870795-Alkanes,
pubmed-meshheading:21870795-Antineoplastic Agents,
pubmed-meshheading:21870795-Binding Sites,
pubmed-meshheading:21870795-Carbamates,
pubmed-meshheading:21870795-Cell Line, Tumor,
pubmed-meshheading:21870795-Drug Design,
pubmed-meshheading:21870795-Drug Screening Assays, Antitumor,
pubmed-meshheading:21870795-Humans,
pubmed-meshheading:21870795-Lactones,
pubmed-meshheading:21870795-Microtubules,
pubmed-meshheading:21870795-Models, Molecular,
pubmed-meshheading:21870795-Molecular Conformation,
pubmed-meshheading:21870795-Paclitaxel,
pubmed-meshheading:21870795-Protein Binding,
pubmed-meshheading:21870795-Pyrones,
pubmed-meshheading:21870795-Solutions,
pubmed-meshheading:21870795-Stereoisomerism,
pubmed-meshheading:21870795-Structure-Activity Relationship,
pubmed-meshheading:21870795-Tubulin
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pubmed:year |
2011
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pubmed:articleTitle |
Design and synthesis of (+)-discodermolide-paclitaxel hybrids leading to enhanced biological activity.
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pubmed:affiliation |
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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