title: Antibacterial and antifungal screening of natural products sourced from Australian fungi and characterisation of pestalactams D-F.
abstract: Eighteen natural products sourced from Australian micro- or macro-fungi were screened for antibacterial and antifungal activity. This focused library was comprised of caprolactams, polyamines, quinones, and polyketides, with additional large-scale isolation studies undertaken in order to resupply previously identified compounds. Chemical investigations of the re-fermented culture from the endophytic fungus Pestalotiopsis sp. yielded three caprolactam analogues, pestalactams D-F, along with larger quantities of the known metabolite pestalactam A, which was methylated using diazomethane to yield 4-O-methylpestalactam A. The chemical structures of the previously undescribed fungal metabolites were determined by analysis of 1D/2D NMR and MS data. The structure of 4-O-methylpestalactam A was confirmed following single crystal X-ray diffraction analysis. The antibacterial and antifungal activity of all compounds was assessed, which identified three compounds, (1S,3R)-austrocortirubin, (1S,3S)-austrocortirubin, and 1-deoxyaustrocortirubin with mild activity (100 μM) against Gram-positive isolates and one compound, 2-hydroxy-6-methyl-8-methoxy-9-oxo-9H-xanthene-1-carboxylic acid, with activity against Cryptococcus neoformans and Cryptococcus gattii at 50 μM.
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Karren D
authors.initials: KD
authors.lastname: Beattie
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Nicola
authors.initials: N
authors.lastname: Ellwood
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Rohitesh
authors.initials: R
authors.lastname: Kumar
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Xinzhou
authors.initials: X
authors.lastname: Yang
authors.affiliation: School of Natural Sciences, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Healy
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Vanida
authors.initials: V
authors.lastname: Choomuenwai
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia.
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Alysha G
authors.initials: AG
authors.lastname: Elliott
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Johnny X
authors.initials: JX
authors.lastname: Huang
authors.affiliation: School of Chemistry & Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Jessica L
authors.initials: JL
authors.lastname: Chitty
authors.affiliation: School of Chemistry & Molecular Biosciences, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Fraser
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, St Lucia, QLD 4072, Australia.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Cooper
authors.affiliation: Eskitis Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia. Electronic address: r.davis@griffith.edu.au.
authors.forename: Rohan A
authors.initials: RA
authors.lastname: Davis
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D001315:Australia; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002209:Caprolactam / Q000031:analogs & derivatives / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D003455:Cryptococcus neoformans / Q000187:drug effects; D018360:Crystallography, X-Ray; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013098:Xylariales / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D001688:Biological Products; C000611165:pestalactam D; C000611166:pestalactam E; C000611167:pestalactam F; D002209:Caprolactam
keywords: Amphisphaeriaceae; Antibacterial; Antifungal; Caprolactam; Fungal natural products; MIC screening; Pestalactam; Pestalactams A–F; Pestalotiopsis; X-ray crystal structure