Hideo Kigoshi

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.

Separation of carcinogenic fraction of bracken fern

Isolation of the carcinogen in the boiling water extract of bracken fern was conducted by following the active principle with a carcinogenicity bioassay. Fractionation of the bracken extract was carried out using adsorption on resin (Amberlite XAD-2 and TOYOPEARL HW-40 (c] and organic solvent extraction. A diet containing each of the fractions was given to 7 female Charles River Sprague-Dawley rats (CD rats) of 4 weeks old, except for the second fraction. All 7 rats given the last carcinogenic fraction developed mammary and intestinal tumors and 5 rats had urinary bladder tumors. Ptaquiloside (PT) which induced mammary cancer in female CD rats and rho-hydroxystyrene glycosides were isolated from this fraction.

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.

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.

Aplyronine A, a potent antitumour macrolide of marine origin, and the congeners aplyronines B-H: Chemistry and biology

Aplyronines A-H are cytotoxic macrolides isolated from the sea hare Aplysia kurodai. Aplyronine A is the major constituent among the aplyronines, and this review concentrates on the results of chemical and biological research into this natural product. The isolation, determination of stereostructure and enantioselective total synthesis of the aplyronines are covered, together with discussion of their antitumour activity and structure-activity relationships, and the three-dimensional X-ray structure of the actin-aplyronine A complex.

ISOLATION AND STEREOSTRUCTURE OF DOLASTATIN I, A CYTOTOXIC CYCLIC HEXAPEPTIDE FROM THE JAPANESE SEA HARE DOLABELLA AURICULARIA

Abstract Dolastatin I ( 1 ), a cyclic hexapeptide containing three kinds of five-membered heterocycles (oxazole, thiazole, and oxazoline), has been isolated from the Japanese sea hare Dolabella auricularia . The gross structure of 1 was elucidated by spectroscopic analysis. The absolute stereostructure of 1 was determined by chiral HPLC analysis of the amino acid components obtained by acid hydrolysis of 1 . Dolastatin I ( 1 ) exhibited cytotoxicity against HeLa S 3 cells with an IC 50 value of 12 μg/mL.

The three-dimensional structure of neohalicholactone, an unusual fatty acid metabolite from the marine sponge halichondria okadai kadota

The three-dimensional structure of the unusual fatty acid metabolite neohalicholactone, isolated from the marine sponge Halinchondria okadai Kadota, has been determined by X-ray crystallography.

Auripyrones A and B, cytotoxic polypropionates from the sea hare Dolabella auricularia: Isolation and structures

Abstract Two new polypropionates, auripyrones A ( 1 ) and B ( 2 ), have been isolated as cytotoxins from the sea hare Dolabella auricularia . The gross structures of 1 and 2 were determined by spectroscopic analysis, and their relative stereochemistry except for the ester moiety of 2 was established on the basis of the NOESY data.

Laurencenyne, a plausible precursor of various nonterpenoid C15-compounds, and neolaurencenyne from the red alga laurencia okamurai

Structural elucidation of two new acetylenic polyenes, laurencenyne 5 and neolaurencenyne 6 isolated from Laurencia okamurai, together with their syntheses, was achieved, suggesting that laurencenyne 5 was a possible precursor of various nonterpenoid C15-compounds in the marine red algae of the genus Laurencia.