Berkelic acid, a novel spiroketal with selective anticancer activity from an acid mine waste fungal extremophile.
Berkeley Pit Lake is an abandoned open-pit copper mine filled with 30 billion gallons of acidic, metal-contaminated water. This harsh environment is proving to be a source of unusual microorganisms that produce novel bioactive metabolites. Bioassay-guided fractionation using signal transduction enzyme assays led to the isolation of the novel spiroketal, berkelic acid 1, and of the known gamma-pyrone, spiciferone A 4. Berkelic acid has shown selective, nanomolar activity against OVCAR-3, an ovarian cancer cell line in the National Cancer Institute cell line screen. The isolation and characterization of these compounds are reported here.
Stierle
Andrea A
AA
Department of Chemistry, Montana Tech of University of Montana, Butte, MT 59701, USA. astierle@mtech.edu
Stierle
Donald B
DB
Kelly
Kal
K
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006574:Heterocyclic Compounds, 2-Ring / Q000737:chemistry; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods / Q000592:standards; D008968:Molecular Conformation; D010407:Penicillium / Q000737:chemistry*; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013141:Spiro Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D014866:Waste Products; D014867:Water / Q000737:chemistry
D000970:Antineoplastic Agents; D006574:Heterocyclic Compounds, 2-Ring; D013141:Spiro Compounds; D014866:Waste Products; C520589:berkelic acid; C520590:spiciferone A; D014867:Water