title: Isolation, synthesis, and biological activity of aphrocallistin, an adenine-substituted bromotyramine metabolite from the Hexactinellida sponge Aphrocallistes beatrix.
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.
authors.affiliation: Center for Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University, Ft. Pierce, Florida 34946, USA. awrigh33@fau.edu
authors.forename: Amy E
authors.initials: AE
authors.lastname: Wright
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Roth
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Hoffman
authors.forename: Daniela B
authors.initials: DB
authors.lastname: Divlianska
authors.forename: Diana
authors.initials: D
authors.lastname: Pechter
authors.forename: Susan H
authors.initials: SH
authors.lastname: Sennett
authors.forename: Esther A
authors.initials: EA
authors.lastname: Guzmán
authors.forename: Patricia
authors.initials: P
authors.lastname: Linley
authors.forename: Peter J
authors.initials: PJ
authors.lastname: McCarthy
authors.forename: Tara P
authors.initials: TP
authors.lastname: Pitts
authors.forename: Shirley A
authors.initials: SA
authors.lastname: Pomponi
authors.forename: John K
authors.initials: JK
authors.lastname: Reed
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D002176:Candida albicans / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D011161:Porifera / Q000737:chemistry*; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D014439:Tyramine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology
chemical_list: C542034:aphrocallistin; D000225:Adenine; D014439:Tyramine