TY - JOUR
T1 - Cytotoxic Microcolin Lipopeptides from the Marine Cyanobacterium Moorea producens
AU - Yu, Hao Bing
AU - Glukhov, Evgenia
AU - Li, Yueying
AU - Iwasaki, Arihiro
AU - Gerwick, Lena
AU - Dorrestein, Pieter C.
AU - Jiao, Bing Hua
AU - Gerwick, William H.
N1 - Funding Information:
This research was supported by the National Key Research and Development Program of China (No. 2018YFC0310900) (H.B.Y.) the National Institutes of Health CA100851 (W.H.G.), and the International Postdoctoral Exchange Fellowship Program (No. 20170092) (H.B.Y.).*%blankline%*
Funding Information:
This research was supported by the National Key Research and Development Program of China (No. 2018YFC0310900) (H.B.Y.), the National Institutes of Health CA100851 (W.H.G.), and the International Postdoctoral Exchange Fellowship Program (No. 20170092) (H.B.Y.). We also thank Y. Su (UCSD Chemistry and Biochemistry Mass Spectrometry Facility) for some of the HRESIMS data and B. Duggan for assistance with NMR technical support.
Publisher Copyright:
Copyright © 2019 American Chemical Society and American Society of Pharmacognosy.
PY - 2019/9/27
Y1 - 2019/9/27
N2 - 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.
AB - 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.
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U2 - 10.1021/acs.jnatprod.9b00549
DO - 10.1021/acs.jnatprod.9b00549
M3 - Article
C2 - 31468974
AN - SCOPUS:85072644493
SN - 0163-3864
VL - 82
SP - 2608
EP - 2619
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 9
ER -
