Isolation, synthesis, and biological activity of aphrocallistin, an adenine-substituted bromotyramine metabolite from the Hexactinellida sponge Aphrocallistes beatrix.
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.
Wright
Amy E
AE
Center for Marine Biomedical and Biotechnology Research, Harbor Branch Oceanographic Institute at Florida Atlantic University, Ft. Pierce, Florida 34946, USA. awrigh33@fau.edu
Roth
Gregory P
GP
Hoffman
Jennifer K
JK
Divlianska
Daniela B
DB
Pechter
Diana
D
Sennett
Susan H
SH
Guzmán
Esther A
EA
Linley
Patricia
P
McCarthy
Peter J
PJ
Pitts
Tara P
TP
Pomponi
Shirley A
SA
Reed
John K
JK
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
C542034:aphrocallistin; D000225:Adenine; D014439:Tyramine