Targeted natural products discovery from marine cyanobacteria using combined phylogenetic and mass spectrometric evaluation.

Abstract

Combined phylogenetic and HPLC-MS-based natural products dereplication methods aimed at identifying cyanobacterial collections containing the potent cytotoxins largazole, dolastatin 10, and symplostatin 1 were developed. The profiling of the phylogeny, chemical space, and antiproliferative activity of cyanobacterial collections served to streamline the prioritization of samples for the discovery of new secondary metabolites. The dereplication methods highlighted the biosynthetic potential and combinatorial pharmacology employed by marine cyanobacteria. We found that largazole was always coproduced with dolastatin 10 or with symplostatin 1 and consequently tested combinations of these agents against colon cancer cells. Combinatorial regimens of largazole and dolastatin 10 aimed at curbing the growth of HCT116 cancer cells showed cooperative activity.

• Authors: Lilibeth A Salvador-Reyes, Niclas Engene, Valerie J Paul, Hendrik Luesch
• Journal: Journal of natural products (J Nat Prod) Vol. 78 Issue 3 Pg. 486-92 (Mar 27 2015) ISSN: 1520-6025 [Electronic] United States
• PMID: 25635943 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biological Products
• Cytotoxins
• Depsipeptides
• Thiazoles
• largazole
• symplostatin 1
• dolastatin 10

Topics

• Biological Products (chemistry, isolation & purification, pharmacology)
• Chromatography, High Pressure Liquid
• Colonic Neoplasms (drug therapy)
• Cyanobacteria (chemistry)
• Cytotoxins (chemistry, isolation & purification, pharmacology)
• Depsipeptides (chemistry)
• HCT116 Cells
• Humans
• Marine Biology
• Molecular Structure
• Nuclear Magnetic Resonance, Biomolecular
• Phylogeny
• Thiazoles (chemistry)