title: Azaphilones from an Acid Mine Extremophile Strain of a Pleurostomophora sp.
abstract: 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).
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Stierle
authors.forename: Donald B
authors.initials: DB
authors.lastname: Stierle
authors.forename: Teri
authors.initials: T
authors.lastname: Girtsman
authors.forename: T C
authors.initials: TC
authors.lastname: Mou
authors.affiliation: HTS Core Facility, Memorial Sloan-Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Christophe
authors.initials: C
authors.lastname: Antczak
authors.affiliation: HTS Core Facility, Memorial Sloan-Kettering Cancer Center , New York, New York 10065, United States.
authors.forename: Hakim
authors.initials: H
authors.lastname: Djaballah
mesh_terms: D001203:Ascomycota / Q000737:chemistry; D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D020170:Caspase 1 / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D058847:Inflammasomes / Q000187:drug effects; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors; D007938:Leukemia / Q000188:drug therapy; D008545:Melanoma / Q000188:drug therapy; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010860:Pigments, Biological / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D011804:Quinolines / Q000737:chemistry / Q000302:isolation & purification; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D000093242:Interleukin-6 Inhibitors
chemical_list: D001578:Benzopyrans; D020170:Caspase 1; D058847:Inflammasomes; D053583:Interleukin-1beta; D010860:Pigments, Biological; D011804:Quinolines; D014409:Tumor Necrosis Factor-alpha; D000093242:Interleukin-6 Inhibitors; C550905:4-(hydroxymethyl)quinoline; C494154:azaphilone; C000607232:berkchaetoazaphilone A; C000607234:berkchaetoazaphilone B; C000607236:berkchaetoazaphilone C