Browsing by Author "Kerr, Russell G."

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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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    Discovery of an isothiazolinone-containing antitubercular natural product Levesquamide
    (American Chemical Society, 2020-05-04) Liang, Libang; Haltli, Bradley; Marchbank, Douglas H.; Fischer, Maike; Kirby, Christopher W.; Correa, Hebelin; Clark, Trevor N.; Gray, Christopher A.; Kerr, Russell G.
    Antitubercular agent levesquamide is a new polyketide-nonribosomal peptide (PK-NRP) hybrid marine natural product isolated from Streptomyces sp. RKND-216. The structure contains a rare isothiazolinone moiety which has only been reported in collismycin SN. Structure elucidation by NMR spectroscopy was a significant challenge due to a deficiency of protons in this aromatic moiety. Therefore, the genome of Streptomyces sp. RKND-216 was sequenced to identify the levesquamide biosynthetic gene cluster (BGC). Analysis of the BGC provided structural insights and guided stable-isotope labeling experiments, which led to the assignment of the fused pyridine-isothiazolinone moiety. The BGC and the labeling experiments provide further insights into the biosynthetic origin of isothiazolinones. Levesquamide exhibited antimicrobial activity in the microplate alamarBlue assay (MABA) and low oxygen recovery assay (LORA) against Mycobacterium tuberculosis H37Rv with minimum inhibitory concentration (MIC) values of 9.65 and 22.28 µM, respectively. Similar activity was exhibited against rifampicin- and isoniazid-resistant M. tuberculosis strains with MIC values of 9.46 and 9.90 µM, respectively. This result suggests levesquamide has a different mode of action against M. tuberculosiscompared to the two first-line antitubercular drugs rifampicin and isoniazid. Furthermore, levesquamide shows no cytotoxicity against the Vero cell line, suggesting it may have a useful therapeutic window.