title: Oxaspirol B with p97 Inhibitory Activity and Other Oxaspirols from Lecythophora sp. FL1375 and FL1031, Endolichenic Fungi Inhabiting Parmotrema tinctorum and Cladonia evansii.
abstract: A new metabolite, oxaspirol D (4), together with oxaspirols B (2) and C (3) were isolated from Lecythophora sp. FL1375, an endolichenic fungus isolated from Parmotrema tinctorum, whereas Lecythophora sp. FL1031 inhabiting the lichen Cladonia evansii afforded oxaspirols A (1), B (2), and C (3). Of these, oxaspirol B (2) showed moderate p97 ATPase inhibitory activity. A detailed characterization of all oxaspirols was undertaken because structures proposed for known oxaspirols have involved incomplete assignments of NMR spectroscopic data leading only to their planar structures. Thus, the naturally occurring isomeric mixture (2a and 2b) of oxaspirol B was separated as their diacetates (5a and 5b) and the structures and absolute configurations of 1, 2a, 2b, 3, and 4 were determined by the application of spectroscopic techniques including two-dimensional NMR and the modified Mosher's ester method. Oxaspirol B (2) and its diacetates 5a and 5b were evaluated for their ATPase inhibitory activities of p97, p97 mutants, and other ATP-utilizing enzymes, and only 2 was found to be active, indicating the requirement of some structural features in oxaspirols for their activity. Additional biochemical and cellular assays suggested that 2 was a reversible, non-ATP competitive, and specific inhibitor of p97.
authors.affiliation: Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona , 250 East Valencia Road, Tucson, Arizona 85706, United States.
authors.forename: E M Kithsiri
authors.initials: EM
authors.lastname: Wijeratne
authors.affiliation: Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona , 250 East Valencia Road, Tucson, Arizona 85706, United States.|Department of Chemistry, Open University of Sri Lanka , Nugegoda 10250, Sri Lanka.
authors.forename: G M Kamal B
authors.initials: GM
authors.lastname: Gunaherath
authors.affiliation: Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona , 250 East Valencia Road, Tucson, Arizona 85706, United States.|Departamento de Química Orgânica, Instituto de Química, UNESP, Universidade Estadual Paulista , Araraquara, Sao Paulo 14800-900, Brazil.
authors.forename: Vanessa M
authors.initials: VM
authors.lastname: Chapla
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: Joseph
authors.initials: J
authors.lastname: Tillotson
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: Fabian
authors.initials: F
authors.lastname: de la Cruz
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: MinJing
authors.initials: M
authors.lastname: Kang
authors.affiliation: School of Plant Sciences, College of Agriculture and Life Sciences, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: Jana M
authors.initials: JM
authors.lastname: U'Ren
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, UNESP, Universidade Estadual Paulista , Araraquara, Sao Paulo 14800-900, Brazil.
authors.forename: Angela R
authors.initials: AR
authors.lastname: Araujo
authors.affiliation: School of Plant Sciences, College of Agriculture and Life Sciences, University of Arizona , Tucson, Arizona 85721, United States.|Department of Ecology and Evolutionary Biology, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: A Elizabeth
authors.initials: AE
authors.lastname: Arnold
authors.affiliation: Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona , Tucson, Arizona 85721, United States.
authors.forename: Eli
authors.initials: E
authors.lastname: Chapman
authors.affiliation: Natural Products Center, School of Natural Resources and the Environment, College of Agriculture and Life Sciences, University of Arizona , 250 East Valencia Road, Tucson, Arizona 85706, United States.
authors.forename: A A Leslie
authors.initials: AA
authors.lastname: Gunatilaka
mesh_terms: D000251:Adenosine Triphosphatases / Q000037:antagonists & inhibitors*; D001203:Ascomycota / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D005431:Florida; D065928:Forests; D008011:Lichens / Q000382:microbiology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D009687:Nuclear Proteins; D013141:Spiro Compounds; C000608905:oxaspirol B; D000251:Adenosine Triphosphatases; C404942:p97 ATPase
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