Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens

  • J Nat Prod. 2019 Sep 27;82(9):2608-2619. doi: 10.1021/acs.jnatprod.9b00549.
Hao-Bing Yu  1  2 ,  Evgenia Glukhov  2 ,  Yueying Li  2 ,  Arihiro Iwasaki  2  3 ,  Lena Gerwick  2 ,  Pieter C Dorrestein  4 ,  Bing-Hua Jiao  1 ,  William H Gerwick  2  4
Affiliations
  • 1. Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences , Second Military Medical University , Shanghai 200433 , People's Republic of China.
  • 2. Center for Marine Biotechnology and Biomedicine , Scripps Institution of Oceanography, University of California, San Diego , La Jolla , California 92093 , United States.
  • 3. Department of Chemistry , Keio University , 3-14-1, Hiyoshi, Kohoku-ku , Yokohama , Kanagawa 223-8522 , Japan.
  • 4. Skaggs School of Pharmacy and Pharmaceutical Sciences , University of California, San Diego , La Jolla , California 92093 , United States.
PMID: 31468974 DOI: 10.1021/acs.jnatprod.9b00549
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.