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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1995-3-10
|
| pubmed:abstractText |
The synthesis and antitumor activities of the novel water soluble camptothecin derivatives 7-[(4-methylpiperazino)methyl]-10,11-(methylenedioxy)-(20S)-campto thecin trifluoroacetate (6) and 7-[(4-methylpiperazino)methyl]-10,11-(ethylenedioxy)-(20S)-camptot hecin trifluoroacetate (7) are described. The solubilities of compounds 6 and 7 were measured to be 4.5 and 5.8 mg/mL, respectively, in pH 5 acetate buffer in contrast to < 0.003 mg/mL for camptothecin in the same buffer. In the purified topoisomerase I cleavable complex enzyme assay, compounds 6 and 7 demonstrated potent inhibition of topoisomerase I with IC50's of 300 and 416 nM, respectively, in comparison to 679 nM for camptothecin and 1028 nM for topotecan. In human tumor cell cytotoxicity assays, compounds 6 and 7 demonstrated potent antitumor activity against ovarian (SKOV3), ovarian with upregulated MDRp-glycoprotein (SKVLB), melanoma (LOX), breast (T47D), and colon (HT29) with IC50's ranging from 0.5 to 102 nM. Compounds 6 and 7 induced tumor regressions in the HT29 human colon tumor xenograft model and demonstrated similar rank order of potency compared to in vitro assay results.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Feb
|
| pubmed:issn |
0022-2623
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
3
|
| pubmed:volume |
38
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
N
|
| pubmed:pagination |
395-401
|
| pubmed:dateRevised |
2010-11-18
|
| pubmed:meshHeading |
pubmed-meshheading:7853331-Animals,
pubmed-meshheading:7853331-Antineoplastic Agents,
pubmed-meshheading:7853331-Camptothecin,
pubmed-meshheading:7853331-Cell Survival,
pubmed-meshheading:7853331-Female,
pubmed-meshheading:7853331-Humans,
pubmed-meshheading:7853331-Mice,
pubmed-meshheading:7853331-Solubility,
pubmed-meshheading:7853331-Topoisomerase I Inhibitors,
pubmed-meshheading:7853331-Tumor Cells, Cultured,
pubmed-meshheading:7853331-Water
|
| pubmed:year |
1995
|
| pubmed:articleTitle |
Synthesis and antitumor activity of novel water soluble derivatives of camptothecin as specific inhibitors of topoisomerase I.
|
| pubmed:affiliation |
Department of Medicinal Chemistry, Glaxo Research Institute, Research Triangle Park, North Carolina 27709.
|
| pubmed:publicationType |
Journal Article
|