Azaphilones from an Acid Mine Extremophile Strain of a Pleurostomophora sp

• Published in: Journal of natural products (Washington, D.C.) D.C.), 2015-12, Vol.78 (12), p.2917-2923
• Main Authors: Stierle, Andrea A, Stierle, Donald B, Girtsman, Teri, Mou, T. C, Antczak, Christophe, Djaballah, Hakim
• Format: Article
• Language: English
• Subjects: Ascomycota - chemistry; Benzopyrans - chemistry; Benzopyrans - isolation & purification; Benzopyrans - pharmacology; Caspase 1 - drug effects; Drug Screening Assays, Antitumor; Humans; Inflammasomes - drug effects; Interleukin-1beta - antagonists & inhibitors; Interleukin-6 - antagonists & inhibitors; Leukemia - drug therapy; Melanoma - drug therapy; Molecular Structure; Nuclear Magnetic Resonance, Biomolecular; Pigments, Biological - chemistry; Pigments, Biological - isolation & purification; Pigments, Biological - pharmacology; Quinolines - chemistry; Quinolines - isolation & purification; Tumor Necrosis Factor-alpha - antagonists & inhibitors
• ISSN: 0163-3864; 1520-6025
• DOI: 10.1021/acs.jnatprod.5b00519

An extremophilic fungus identified as a Pleurostomophora sp. was isolated from the Berkeley Pit, an acid mine waste lake. When grown in liquid culture, the fungus produced berkchaetoazaphilones A–C (1, 2, and 5), the red pigment berkchaetorubramine (6), and the known compound 4-(hydroxymethyl)­quinoline. These compounds were evaluated as inhibitors of matrix metalloproteinase-3, caspase-1, and proinflammatory cytokine production in induced THP-1 cells. Berkchaetoazaphilone B (2) inhibited IL-1β, TNFα, and IL-6 production in the induced inflammasome assay and was cytotoxic toward human retinoblastoma cell line Y79 (IC50 = 1.1 μM), leukemia cell lines CCRF-CEM and SR, and the melanoma cell line LOX IMVI (IC50 = 10 μM).