title: Cytotoxic halogenated macrolides and modified peptides from the apratoxin-producing marine cyanobacterium Lyngbya bouillonii from Guam.
abstract: Collections of the marine cyanobacterium Lyngbya bouillonii from shallow patch reefs in Apra Harbor, Guam, afforded three hitherto undescribed analogues of the glycosidic macrolide lyngbyaloside, namely, 2-epi-lyngbyaloside (1) and the regioisomeric 18E- and 18Z-lyngbyalosides C (2 and 3). Concurrently we discovered two new analogues of the cytoskeletal actin-disrupting lyngbyabellins, 27-deoxylyngbyabellin A (4) and lyngbyabellin J (5), a novel macrolide of the laingolide family, laingolide B (6), and a linear modified peptide, lyngbyapeptin D (7), along with known lyngbyabellins A and B, lyngbyapeptin A, and lyngbyaloside. The structures of 1-7 were elucidated by a combination of NMR spectroscopic and mass spectrometric analysis. Compounds 1-6 were either brominated (1-3) or chlorinated (4-6), consistent with halogenation being a hallmark of many marine natural products. All extracts derived from these L. bouillonii collections were highly cytotoxic due to the presence of apratoxin A or apratoxin C. Compounds 1-5 showed weak to moderate cytotoxicity to HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells.
authors: Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA.
authors: Susan
authors: S
authors: Matthew
authors: Lilibeth A
authors: LA
authors: Salvador
authors: Peter J
authors: PJ
authors: Schupp
authors: Valerie J
authors: VJ
authors: Paul
authors: Hendrik
authors: H
authors: Luesch
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000458:Cyanobacteria / Q000737:chemistry*; D047630:Depsipeptides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006141:Guam; D019073:HT29 Cells; D006367:HeLa Cells; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008235:Lyngbya Toxins / Q000737:chemistry*; D018942:Macrolides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D008386:Marine Biology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D006846:Hydrocarbons, Halogenated; D008235:Lyngbya Toxins; D018942:Macrolides; C470919:apratoxin C; C410925:lyngbyabellin A