Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens

Hao Bing Yu, Evgenia Glukhov, Yueying Li, Arihiro Iwasaki, Lena Gerwick, Pieter C. Dorrestein, Bing Hua Jiao, William H. Gerwick

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Abstract

Nine new linear lipopeptides, microcolins E-M (1-9), together with four known related compounds, microcolins A-D (10-13), were isolated from the marine cyanobacterium Moorea producens using bioassay-guided and LC-MS/MS molecular networking approaches. Catalytic hydrogenation of microcolins A-D (10-13) yielded two known compounds, 3,4-dihydromicrocolins A and B (14, 15), and two new derivatives, 3,4-dihydromicrocolins C and D (16, 17), respectively. The structures of these new compounds were determined by a combination of spectroscopic and advanced Marfey's analysis. Structurally unusual amino acid units, 4-methyl-2-(methylamino)pent-3-enoic (Mpe) acid and 2-amino-4-methylhexanoic acid (N-Me-homoisoleucine), in compounds 1-3 and 8, respectively, are rare residues in naturally occurring peptides. These metabolites showed significant cytotoxic activity against H-460 human lung cancer cells with IC50 values ranging from 6 nM to 5.0 μM. The variations in structure and attendant biological activities provided fresh insights concerning structure-activity relationships for the microcolin class of lipopeptides.

Original languageEnglish
Pages (from-to)2608-2619
Number of pages12
JournalJournal of Natural Products
Volume82
Issue number9
DOIs
Publication statusPublished - 2019 Sep 27

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ASJC Scopus subject areas

  • Analytical Chemistry
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Drug Discovery
  • Complementary and alternative medicine
  • Organic Chemistry

Cite this

Yu, H. B., Glukhov, E., Li, Y., Iwasaki, A., Gerwick, L., Dorrestein, P. C., Jiao, B. H., & Gerwick, W. H. (2019). Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens. Journal of Natural Products, 82(9), 2608-2619. https://doi.org/10.1021/acs.jnatprod.9b00549