Abstract
A new adenine-substituted bromotyrosine-derived metabolite designated as aphrocallistin (1) has been isolated from the deep-water Hexactinellida sponge Aphrocallistes beatrix. Its structure was elucidated on the basis of spectral data and confirmed through a convergent, modular total synthetic route that is amenable toward future analogue preparation. Aphrocallistin inhibits the growth of a panel of human tumor cell lines with IC(50) values ranging from 7.5 to >100 microM and has been shown to induce G1 cell cycle arrest in the PANC-1 pancreatic carcinoma cell line. Aphrocallistin has been fully characterized in the NCI cancer cell line panel and has undergone in vitro ADME pharmacological profiling.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenine / analogs & derivatives*
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Adenine / chemical synthesis
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Adenine / isolation & purification
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Adenine / pharmacology
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Animals
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Candida albicans / drug effects
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Cell Cycle / drug effects
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Drug Screening Assays, Antitumor
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Humans
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Inhibitory Concentration 50
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Methicillin-Resistant Staphylococcus aureus / drug effects
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Microbial Sensitivity Tests
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Molecular Structure
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Nuclear Magnetic Resonance, Biomolecular
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Porifera / chemistry*
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Pseudomonas aeruginosa / drug effects
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Tyramine / analogs & derivatives*
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Tyramine / chemical synthesis
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Tyramine / isolation & purification
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Tyramine / pharmacology
Substances
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aphrocallistin
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Adenine
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Tyramine