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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4A
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pubmed:dateCreated |
1998-9-1
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pubmed:abstractText |
Paclitaxel shows interesting clinical activity against several tumors. However, its poor solubility is an important limitation: Cremophor EL used for intravenous administration is responsible for hypersensitivity reactions. In order to improve solubility while preserving the activity, we have synthesized new paclitaxel amino acid derivatives substituted with a glutaryl group at the 2' position followed by the reaction of a peptide link between the carboxyl and the amino terminal group of the amino acid. The derivatives were cytotoxic in vitro against many sensitive cell lines. They also increased G2+M phase arrest. Moreover, these derivatives were stable for over a year and showed a better solubility in water than the parent compound. The ester linkage is hydrolysed in slightly acid lysosomal conditions to free paclitaxel which binds to tubulin.
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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:issn |
0250-7005
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2711-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9703933-Amino Acids,
pubmed-meshheading:9703933-Animals,
pubmed-meshheading:9703933-Asparagine,
pubmed-meshheading:9703933-Cell Cycle,
pubmed-meshheading:9703933-Cell Survival,
pubmed-meshheading:9703933-Drug Design,
pubmed-meshheading:9703933-Female,
pubmed-meshheading:9703933-Glutamine,
pubmed-meshheading:9703933-Glycerol,
pubmed-meshheading:9703933-Glycine,
pubmed-meshheading:9703933-Humans,
pubmed-meshheading:9703933-Melanoma, Experimental,
pubmed-meshheading:9703933-Mice,
pubmed-meshheading:9703933-Molecular Structure,
pubmed-meshheading:9703933-Ovarian Neoplasms,
pubmed-meshheading:9703933-Paclitaxel,
pubmed-meshheading:9703933-Serine,
pubmed-meshheading:9703933-Solubility,
pubmed-meshheading:9703933-Structure-Activity Relationship,
pubmed-meshheading:9703933-Tumor Cells, Cultured,
pubmed-meshheading:9703933-Water
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pubmed:articleTitle |
New active paclitaxel amino acids derivatives with improved water solubility.
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pubmed:affiliation |
Department of Biochemistry, Faculty of Medicine, Université Laval, Sie-Foy, Québec, Canada.
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pubmed:publicationType |
Journal Article,
Comparative Study
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