title: 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: †Department of Medicinal Chemistry, University of Florida, 1345 Center Drive, Gainesville, Florida 32610, United States.|‡Marine Science Institute, College of Science, University of the Philippines, Diliman, Velasquez Street, Quezon City 1101, Philippines.
authors: Lilibeth A
authors: LA
authors: Salvador-Reyes
authors: §Smithsonian Marine Station, 701 Seaway Drive, Fort Pierce, Florida 34949, United States.|⊥Department of Biological Sciences, Florida International University, Miami, Florida 33199, United States.
authors: Niclas
authors: N
authors: Engene
authors: §Smithsonian Marine Station, 701 Seaway Drive, Fort Pierce, Florida 34949, United States.
authors: Valerie J
authors: VJ
authors: Paul
authors: †Department of Medicinal Chemistry, University of Florida, 1345 Center Drive, Gainesville, Florida 32610, United States.|∥Center for Natural Products, Drug Discovery and Development (CNPD3), University of Florida, 1345 Center Drive, Gainesville, Florida 32610, United States.
authors: Hendrik
authors: H
authors: Luesch
mesh_terms: D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D003110:Colonic Neoplasms / Q000188:drug therapy; D000458:Cyanobacteria / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D047630:Depsipeptides / Q000737:chemistry; D045325:HCT116 Cells; D006801:Humans; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010802:Phylogeny; D013844:Thiazoles / Q000737:chemistry
chemical_list: D001688:Biological Products; D003603:Cytotoxins; D047630:Depsipeptides; D013844:Thiazoles; C527895:largazole; C115534:symplostatin 1; C064570:dolastatin 10
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