Caspase-1 and-3 Inhibiting Drimane Sesquiterpenoids from the Extremophilic Fungus Penicillium solitum

Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA.
Journal of Natural Products (Impact Factor: 3.8). 02/2012; 75(2):262-6. DOI: 10.1021/np200528n
Source: PubMed


Two new drimane sesquiterpene lactones and one new tricarboxylic acid derivative were isolated from the Berkeley Pit extremophilic fungus Penicillium solitum. The structures of these compounds were deduced by spectroscopic analysis. Berkedrimanes A and B inhibited the signal transduction enzymes caspase-1 and caspase-3 and mitigated the production of interleukin 1-β in the induced THP-1 (pro-monocytic leukemia cell line) assay. © 2012 The American Chemical Society and American Society of Pharmacognosy.

Download full-text


Available from: Donald B Stierle, Oct 01, 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpurides B and C (1 and 2, resp.), two new sesquiterpene alcohol esters generated from a drimane-type sesquiterpenoid lactone and an amino acid, together with two known analogs, berkedrimane B (3) and purpuride (4), were isolated from the aciduric fungus Penicillium purpurogenum JS03-21. Their structures were elucidated by spectroscopic analysis, X-ray single-crystal diffraction, and application of Marfey's method. Compounds 1-4 showed modest antifungal activities against Candida albicans with MIC values in the range of 1.2-3.3 μM. Compounds 1 and 2 showed moderate antimicrobial activities against Enterobacter aerogenes and Pseudomonas aeruginosa with MIC values in the range of 1.2-2.6 μM.
    No preview · Article · Jul 2013 · Chemistry & Biodiversity
  • [Show abstract] [Hide abstract]
    ABSTRACT: The extremophilic microbes of the Berkeley Pit Lake are a valuable source of new and interesting secondary metabolites. It is of particular interest that these acidophilic microbes produce small molecule inhibitors of pathways associated with low pH and high Eh. These same small molecules also inhibit molecular pathways induced by reactive oxygen species (ROS) and inflammation in mammalian cells. Low pH is a hallmark of inflammation and high Eh is one of ROS, so the suitability of this collection as a source of bioactive metabolites is actually quite biorational. Compound isolation was guided by inhibition of caspase-1 and matrix metalloproteinase-3, and active compounds were sent to the National Cancer Institute-Developmental Therapeutics Program and Memorial Sloan Kettering Cancer center for evaluation as either antiproliferative or cytotoxic agents.
    No preview · Article · Jul 2014 · Natural product communications
  • [Show abstract] [Hide abstract]
    ABSTRACT: The first asymmetric total synthesis of (+)-iresin (4), a historically important ent-Drimane sesquiterpene lactone, was realized from aldehyde 3 via cyclic orthoester 6 in 5 steps. Notable transformations in this synthesis include a tandem trifluoroperacetic acid (TFPAA)-mediated Baeyer-Villiger oxidation-olefin epoxidation-epoxy ester cyclization, regioselective Burgess dehydration, and regioselective Fétizon oxidative lactonization.
    No preview · Article · Apr 2015 · The Journal of Organic Chemistry
Show more