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

Research output: Contribution to journalArticle

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

Fingerprint

Lipopeptides
Cyanobacteria
Hydrogenation
Bioassay
Structure-Activity Relationship
Metabolites
Bioactivity
Biological Assay
Inhibitory Concentration 50
Lung Neoplasms
Cells
Derivatives
Amino Acids
Peptides
Acids
microcolin A
4-methylhexanoic acid
desintegron B
8-1 compound
pent-2-enoic acid

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., ... 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

Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens. / Yu, Hao Bing; Glukhov, Evgenia; Li, Yueying; Iwasaki, Arihiro; Gerwick, Lena; Dorrestein, Pieter C.; Jiao, Bing Hua; Gerwick, William H.

In: Journal of Natural Products, Vol. 82, No. 9, 27.09.2019, p. 2608-2619.

Research output: Contribution to journalArticle

Yu, HB, Glukhov, E, Li, Y, Iwasaki, A, Gerwick, L, Dorrestein, PC, Jiao, BH & Gerwick, WH 2019, 'Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens', Journal of Natural Products, vol. 82, no. 9, pp. 2608-2619. https://doi.org/10.1021/acs.jnatprod.9b00549
Yu, Hao Bing ; Glukhov, Evgenia ; Li, Yueying ; Iwasaki, Arihiro ; Gerwick, Lena ; Dorrestein, Pieter C. ; Jiao, Bing Hua ; Gerwick, William H. / Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens. In: Journal of Natural Products. 2019 ; Vol. 82, No. 9. pp. 2608-2619.
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