Kiyotake Suenaga

Structural determination of pteriatoxins A, B and C, extremely potent toxins from the bivalve Pteria penguin

Abstract Pteriatoxins A, B and C, extremely potent toxins, were isolated from the Okinawan bivalve Pteria penguin. Their structures were determined based on NMR and MS/MS spectral analyses. Pteriatoxins have polyether macrocycles composed of 6,7-spiro, 5,6-bicyclo and 6,5,6-trispiro ketal rings, the same as in pinnatoxins.

Pinnatoxins B and C, the most toxic components in the pinnatoxin series from the Okinawan bivalve Pinna muricata

Abstract Pinnatoxins B and C, the most toxic components in the pinnatoxin series, were successfully purified from the Okinawan bivalve Pinna muricata . Their gross structures were determined based on NMR and MS/MS spectral analyses. Their stereostructures were mainly determined by transformation reactions. Pinnatoxins B and C, C-34 epimers of each other, have an amphoteric macrocycle composed of 6,7-spiro, 5,6-bicyclo and 6,5,6-trispiro ketal rings, the same as in pinnatoxins A and D.

Bisebromoamide, a Potent Cytotoxic Peptide from the Marine Cyanobacterium Lyngbya sp.: Isolation, Stereostructure, and Biological Activity

A novel cytotoxic peptide, termed bisebromoamide (1), has been isolated from the marine cyanobacterium Lyngbya sp. Its planar structure was determined by 1D and 2D NMR spectroscopy. The absolute stereostructure of 1 was determined by chemical degradation followed by chiral HPLC analysis. Bisebromoamide (1) exhibited potent protein kinase inhibition: the phosphorylation of ERK in NRK cells by PDGF-stimulation was selectively inhibited by treatment with 10-0.1 microM of 1.

Marine Natural Product Aurilide Activates the OPA1-Mediated Apoptosis by Binding to Prohibitin

Aurilide is a potent cytotoxic marine natural product that induces apoptosis in cultured human cells at the picomolar to nanomolar range; however, its mechanism of action has been unknown. Results of the present study showed that aurilide selectively binds to prohibitin 1 (PHB1) in the mitochondria, activating the proteolytic processing of optic atrophy 1 (OPA1) and resulting in mitochondria-induced apoptosis. The mechanism of aurilide cytotoxicity suggests that PHB1 is an apoptosis-regulating protein amenable to modulation by small molecules. Aurilide may serve as a small-molecule tool for studies of mitochondria-induced apoptosis.

Biselyngbyaside, a Macrolide Glycoside from the Marine Cyanobacterium Lyngbya sp.

Bioassay-guided fractionation of the cytotoxic constituents of the marine cyanobacterium Lyngbya sp. led to the isolation of biselyngbyaside (1), a new 18-membered macrolide glycoside. The structure of 1 was established by spectroscopic analysis including 2D-NMR techniques and by synthetic studies. Biselyngbyaside (1) exhibits broad-spectrum cytotoxicity in a human tumor cell line panel.

Isolation and structures of haterumalides NA, NB, NC, ND, and NE, novel macrolides from an Okinawan Sponge Ircinia sp.

Abstract Novel macrolides, haterumalides NA ( 1 ), NB ( 2 ), NC ( 3 ), ND ( 4 ), and NE ( 5 ), were isolated from an Okinawan sponge Ircinia sp. The absolute stereostructure of 1 was determined by spectroscopic analysis and modified Moshers method. Haterumalide NA ( 1 ) showed cytotoxicity against P388 cells and acute toxicity against mice.

Cytotoxicity and actin-depolymerizing activity of aplyronine A, a potent antitumor macrolide of marine origin, and its analogs

Abstract Artificial analogs of aplyronine A ( 1 ), a potent antitumor macrolide, were synthesized and structure–activity (cytotoxicity and actin-depolymerizing activity) relationships were investigated; the side-chain in 1 was found to play a key role in both biological activities.

Cytotoxicity and actin depolymerizing activity of aplyronine A, a potent antitumor macrolide of marine origin, and the natural and artificial analogs

Abstract The artificial analogs of aplyronine A ( 1 ), a potent cytotoxic and antitumor macrolide, were synthesized and the structure-activity (cytotoxicity and actin depolymerizing activity) studies were performed; the side chain portion in 1 was found to play a key role in both biological activities.

Cell-morphology profiling of a natural product library identifies bisebromoamide and miuraenamide A as actin filament stabilizers

Natural products provide a rich source of biological tools, but elucidating their molecular targets remains challenging. Here we report a cell morphological profiling of a natural product library, which permitted the identification of bisebromoamide and miuraenamide A as actin filament stabilizers. Automated high-content image analysis showed that these two structurally distinct marine natural products induce morphological changes in HeLa cells similar to those induced by known actin-stabilizing compounds. Bisebromoamide and miuraenamide A stabilized actin filaments in vitro, and fluorescein-conjugated bisebromoamide localized specifically to actin filaments in cells. Cell morphological profiling was also used to identify actin-stabilizing or -destabilizing natural products from marine sponge extracts, leading to the isolation of pectenotoxin-2 and lyngbyabellin C. Overall, the results demonstrate that high-content imaging of nuclei and cell shapes offers a sensitive and convenient method for detecting and isolating molecules that target actin.

Isolation and stereostructure of aurilide, a novel cyclodepsipeptide from the Japanese sea hare Dolabella auricularia

Abstract Aurilide ( 1 ), a new 26-membered cyclodepsipeptide, has been isolated from the Japanese sea hare Dolabella auricularia . The gross structure of 1 was established by spectroscopic analysis. The absolute stereostructure of 1 was determined by HPLC analysis of amino acid components and isoleucic acid obtained from acidic hydrolysis of 1 and by the enantioselective synthesis of the tris( p -bromobenzoate) 3 derived from the dihydroxy acid moiety.