Browsing by Author "Johnson, John A."

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    Antimycobacterial 1,4-napthoquinone natural products from Moneses uniflora
    (Elsevier, 2018-10) Li, Haoxin; Bos, Allyson; Jean, Stéphanie; Webster, Duncan; Robichaud, Gilles A.; Johnson, John A.; Gray, Christopher A.
    A new 1,4-naphthoquinone derivative, 5,8-dihydro-3-hydroxychimaphilin (4) and five known compounds (1, 2 and 5–7) were isolated from an extract of the Canadian medicinal plant Moneses uniflora that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structure of 4 was established through analysis of NMR and MS data and the absolute configuration of the glycone of 5 was determined by chemical transformation and comparison with standards prepared from D- and L-glucose. All compounds isolated were screened against Mycobacterium tuberculosis (H37Ra) and the mammalian HEK 293 cell line and, with the exception of compounds 5 and 7, exhibited marked selectivity in their bioactivity: Compound 1 exhibited potent antimycobacterial activity (IC50 of 5.4 μM) and moderate cytotoxicity (IC50 of 30 μM); compounds 2, 4 and 6 showed moderate antimycobacterial activity (IC50 values from 28 – 47 μM) without affecting the viability of mammalian cells; compound 5 displayed moderate activity in both assays (IC50 values of 44 and 55 μM respectively); and compound 7 was not active in either assay. These data suggest that the Moneses napthaquinone derivatives elicit biological responses in mycobacterial and mammalian cells through disparate modes of action that warrant further investigation
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    Caryophyllene sesquiterpenes from a Chaetomium globosum endophyte of the Canadian Medicinal plant Empetrum nigrum
    (American Chemical Society, 2023-06-02) Morehouse, Nicholas J.; Clark, Trevor N.; Kerr, Russell G.; Johnson, John A.; Gray, Christopher A.
    Punctaporonins T (1) and U (2), new caryophyllene sesquiterpenes, were isolated with three known punctaporonins, A (3), B (4), and C (5), from the endophytic fungus Chaetomium globosum (TC2-041). The structures and relative configurations of punctaporonins T and U were elucidated based on a combination of HRESIMS, 1D/2D NMR spectroscopic analysis, and X-ray diffraction analysis whilst their absolute configuration is presumed to be consistent with the co-isolated 3–5 on biogenetic arguments. Compound 1 showed weak inhibitory activity against both Mycobacterium tuberculosis and Staphylococcus aureus.
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    Isolation of an antimicrobial racemic phenalenone derivative from a marine-derived Penicillium sp. fungus
    (Canadian Science Publishing, 2023-10-30) Morehouse, Nicholas J.; Graham, Kelsie M.; Cox, Samantha L.; Johnson, John A.; Gray, Christopher A.
    A new phenalenone derivative, 2,4,6,9-tetrahydroxy-7-methyl-2-prenyl-1H-phenalene 1,3(2H)-dione (1), was isolated from the ethyl acetate extract of a marine derived Penicillium sp. fungus that exhibited a unique antimicrobial activity profile. The planar structure of 1 was determined through a combination of 1D and 2D NMR experiments, and circular dichroism and polarimetry indicated that it was isolated as a racemic mixture of enantiomers. The antimicrobial activity of 1 was assessed against a panel of Gram-positive and Gram-negative bacteria and fungal strains and it was found to selectively inhibit the growth of Staphylococcus aureus and Mycobacterium tuberculosis. Keywords: Phenalenone, Penicillium, Natural product, Antimicrobial
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    Tolypocaibols: Antibacterial lipopeptaibols from a Tolypocladium sp. endophyte of the marine macroalga Spongomorpha arcta
    (American Chemical Society, 2023-06-14) Morehouse, Nicholas J.; Flewelling, Andrew J.; Liu, Dennis Y.; Cavanagh, Hannah; Linington, Roger G.; Johnson, John A.; Gray, Christopher A.
    Two new lipopeptaibols, tolypocaibols A (1) and B (2), and the mixed NRPS-polyketide shikimate natural product maximiscin [(P/M)-3)] were isolated from a Tolypocladium sp. fungal endophyte of the marine alga Spongomorpha arcta. Analysis of NMR and mass spectrometry data revealed the amino acid sequences of the lipopeptaibols, which both comprise 11 residues with a valinol C-terminus and a decanoyl acyl chain at the N-terminus. The configuration of the amino acids was determined by Marfey’s analysis. Tolypocaibols A (1) and B (2) showed moderate, selective inhibition against Gram-positive and acid-fast strains, while maximiscin [(P/M)-3)] showed moderate, broad-spectrum inhibition.