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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
10
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pubmed:dateCreated |
1998-5-28
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pubmed:abstractText |
A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (1b) directed at maintaining the (Z)-stilbene relationship of the olefin diphenyl substituents led to synthesis of a potent cancer cell growth inhibitor designated phenstatin (3b). Initially phenstatin silyl ether (3a) was unexpectedly obtained by Jacobsen oxidation of combretastatin A-4 silyl ether (1c --> 3a), and the parent phenstatin (3b) was later synthesized (6a --> 3a --> 3b) in quantity. Phenstatin was converted to the sodium phosphate prodrug (3d) by a dibenzyl phosphite phosphorylation and subsequent hydrogenolysis sequence (3b --> 3c --> 3d). Phenstatin (3b) inhibited growth of the pathogenic bacterium Neisseriagonorrhoeae and was a potent inhibitor of tubulin polymerization and the binding of colchicine to tubulin comparable to combretastatin A-4 (1b). Interestingly, the prodrugs were found to have reduced activity in these biochemical assays. While no significant tubulin activity was observed with the phosphorylated derivative of combretastatin A-4 (1d), phosphate 3d retained detectable inhibitory effects in both assays.
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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 |
May
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pubmed:issn |
0022-2623
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
7
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pubmed:volume |
41
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1688-95
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9572894-Animals,
pubmed-meshheading:9572894-Anti-Bacterial Agents,
pubmed-meshheading:9572894-Antineoplastic Agents, Phytogenic,
pubmed-meshheading:9572894-Benzophenones,
pubmed-meshheading:9572894-Cattle,
pubmed-meshheading:9572894-Cell Division,
pubmed-meshheading:9572894-Colchicine,
pubmed-meshheading:9572894-Crystallography, X-Ray,
pubmed-meshheading:9572894-Drug Screening Assays, Antitumor,
pubmed-meshheading:9572894-Humans,
pubmed-meshheading:9572894-Leukemia P388,
pubmed-meshheading:9572894-Macromolecular Substances,
pubmed-meshheading:9572894-Molecular Structure,
pubmed-meshheading:9572894-Neisseria gonorrhoeae,
pubmed-meshheading:9572894-Phosphoric Acid Esters,
pubmed-meshheading:9572894-Prodrugs,
pubmed-meshheading:9572894-Protein Binding,
pubmed-meshheading:9572894-Tubulin,
pubmed-meshheading:9572894-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
Antineoplastic agents. 379. Synthesis of phenstatin phosphate.
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pubmed:affiliation |
Cancer Research Institute and Department of Chemistry, Arizona State University, Tempe, Arizona 85287-1604, USA.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, Non-P.H.S.
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