Conglobatins B-E: cytotoxic analogues of the C 2 -symmetric macrodiolide conglobatin

Chemical investigation of a previously unreported indigenous Australian Streptomyces strain MST-91080 has identified six novel analogues related to the oxazole-pendanted macrodiolide, conglobatin. Phylogenetic analysis of the 16S rRNA gene sequence identified MST-91080 as a species of Streptomyces,...

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Bibliographic Details
Published in:Journal of antibiotics 2020-11, Vol.73 (11), p.756
Main Authors: Lacey, Heather J, Booth, Thomas J, Vuong, Daniel, Rutledge, Peter J, Lacey, Ernest, Chooi, Yit-Heng, Piggott, Andrew M
Format: Article
Language:English
Subjects:
Cell Line, Tumor - drug effects
Cytotoxins - chemistry
Cytotoxins - isolation & purification
Cytotoxins - pharmacology
Humans
Magnetic Resonance Spectroscopy
Molecular Structure
Oxazoles - chemistry
Oxazoles - isolation & purification
Streptomyces - chemistry
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Summary:Chemical investigation of a previously unreported indigenous Australian Streptomyces strain MST-91080 has identified six novel analogues related to the oxazole-pendanted macrodiolide, conglobatin. Phylogenetic analysis of the 16S rRNA gene sequence identified MST-91080 as a species of Streptomyces, distinct from reported conglobatin producer, Streptomyces conglobatus ATCC 31005. Conglobatins B-E diverge from conglobatin through differing patterns of methylation on the macrodiolide skeleton. The altered methyl positions suggest a deviation from the published biosynthetic pathway, which proposed three successive methylmalonyl-CoA extender unit additions to the conglobatin monomer. Conglobatins B1, C1 and C2 exhibited more potent cytotoxic activity selectively against the NS-1 myeloma cell line (IC 0.084, 1.05 and 0.45 µg ml , respectively) compared with conglobatin (IC 1.39 µg ml ).
ISSN:1881-1469
DOI:10.1038/s41429-020-0332-3