title: Cyclic depsipeptides, grassypeptolides D and E and Ibu-epidemethoxylyngbyastatin 3, from a Red Sea Leptolyngbya cyanobacterium.
abstract: Two new grassypeptolides and a lyngbyastatin analogue, together with the known dolastatin 12, have been isolated from field collections and laboratory cultures of the marine cyanobacterium Leptolyngbya sp. collected from the SS Thistlegorm shipwreck in the Red Sea. The overall stereostructures of grassypeptolides D (1) and E (2) and Ibu-epidemethoxylyngbyastatin 3 (3) were determined by a combination of 1D and 2D NMR experiments, MS analysis, Marfey's methodology, and HPLC-MS. Compounds 1 and 2 contain 2-methyl-3-aminobutyric acid and 2-aminobutyric acid, while biosynthetically distinct 3 contains 3-amino-2-methylhexanoic acid and the β-keto amino acid 4-amino-2,2-dimethyl-3-oxopentanoic acid (Ibu). Grassypeptolides D (1) and E (2) showed significant cytotoxicity to HeLa (IC₅₀ = 335 and 192 nM, respectively) and mouse neuro-2a blastoma cells (IC₅₀ = 599 and 407 nM, respectively), in contrast to Ibu-epidemethoxylyngbyastatin 3 (neuro-2a cells, IC₅₀ > 10 μM) and dolastatin 12 (neuro-2a cells, IC₅₀ > 1 μM).
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Corvallis, Oregon 97331, USA.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Thornburg
authors.forename: Muralidhara
authors.initials: M
authors.lastname: Thimmaiah
authors.forename: Lamiaa A
authors.initials: LA
authors.lastname: Shaala
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Hau
authors.forename: Jay M
authors.initials: JM
authors.lastname: Malmo
authors.forename: Jane E
authors.initials: JE
authors.lastname: Ishmael
authors.forename: Diaa T A
authors.initials: DT
authors.lastname: Youssef
authors.forename: Kerry L
authors.initials: KL
authors.lastname: McPhail
mesh_terms: D000818:Animals; 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; D006367:HeLa Cells; D006801:Humans; D019156:Indian Ocean; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; C561846:Ibu-epidemethoxylyngbyastatin 3; D010456:Peptides, Cyclic; C115556:dolastatin 12; C561844:grassypeptolide D; C561845:grassypeptolide E