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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
17
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pubmed:dateCreated |
1995-9-27
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pubmed:abstractText |
The potential therapeutic application of the naturally occurring, cytotoxic pseudoguaianolide sesquiterpene lactone ambrosin is limited by its aqueous insolubility. A number of water-soluble ambrosin derivatives have therefore been prepared for potential use as prodrugs. Michael addition of several secondary amines to both the alpha,beta-unsaturated ketone and alpha-methylene lactone moieties of ambrosin afforded tertiary amine diadducts that were converted to water-soluble hydrochloride salts. The salt of the bis-piperidine adduct proved to be the most potent, producing cytotoxic activity only slightly less potent than that of ambrosin itself in a variety of human cancer cell cultures. The sodium salt of the bis-sulfonic acid derivative of ambrosin was inactive, while the sodium salt of the bis-sulfinic acid analog had low activity. Biological evaluation of several ambrosin analogs with reduced and/or isomerized alpha,beta-unsaturated ketone and alpha-methylene lactone moieties demonstrated the importance of both of these functional groups for biological activity.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0022-2623
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
18
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pubmed:volume |
38
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3407-10
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:7650694-Antineoplastic Agents,
pubmed-meshheading:7650694-Drug Screening Assays, Antitumor,
pubmed-meshheading:7650694-Humans,
pubmed-meshheading:7650694-Magnetic Resonance Spectroscopy,
pubmed-meshheading:7650694-Prodrugs,
pubmed-meshheading:7650694-Sesquiterpenes,
pubmed-meshheading:7650694-Tumor Cells, Cultured
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pubmed:year |
1995
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pubmed:articleTitle |
Synthesis and cytotoxicity of water-soluble ambrosin prodrug candidates.
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pubmed:affiliation |
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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