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Caspase-1 Inhibitors from an Extremophilic Fungus That Target Specific Leukemia Cell Lines.
MedLine Citation:
PMID:  22295871     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Berkeley Pit Lake, Butte, Montana, is a 540 m deep abandoned open-pit copper mine filled with over 140 billion liters of acidic, metal-sulfate-contaminated water. This harsh environment has yielded several microorganisms that produce interesting biologically active compounds. Several polyketide metabolites including the new berkazaphilones A (1) and B (2) and octadienoic acid derivatives berkedienoic acid (13) and berkedienolactone (15), as well as previously reported azaphilone 4, vermistatin (6), dihydrovermistatin (7), penisimplicissin (8), aldehyde 9, and methylparaconic acid (11), were isolated from a culture broth of Penicillium rubrum taken from a depth of 270 m. The structures of these compounds were deduced by interpretation of spectroscopic data. The compounds were isolated either for their inhibition of the signal transduction enzyme caspase-1 or because of their structural similarity to these inhibitors. Selected compounds were further evaluated for their ability to inhibit interleukin-1β production by inflammasomes in induced THP-1 cells. Berkazaphilones B (2) and C (4) and vermistatin analogue penisimplicissin (8) exhibited selective activity against leukemia cancer cell lines in the National Cancer Institute 60 human cell line assay.
Authors:
Andrea A Stierle; Donald B Stierle; Teri Girtsman
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-2-1
Journal Detail:
Title:  Journal of natural products     Volume:  -     ISSN:  1520-6025     ISO Abbreviation:  -     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-2-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7906882     Medline TA:  J Nat Prod     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Biomedical and Pharmaceutical Sciences, The University of Montana , Missoula, Montana 59812, United States.
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