Katsuhiko Minoura

Novel antitumour metabolites produced by a fungal strain from a sea hare

Pericosines A (1) and B (2), and macrosphelides E - H (3 – 6) have been isolated, along with known macrosphelide C (7), from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and their structures have been established on the basis of spectral analyses. Compounds 1 and 2 exhibited significant inhibitory activity in vitro against tumour cells, and the former also showed significant in vivo tumour-inhibitory activity.

Cytotoxic cytochalasans from a Penicillium species separated from a marine alga

Abstract New cytochalasans, penochalasins D–H, have been isolated along with chaetoglobosin O from a strain of Penicillium sp. originally separated from the marine alga Enteromorpha intestinalis , and their stereostructures have been established on the basis of spectral analyses. All the compounds exhibited significant cytotoxicity against cultured P388 cells.

Potent cytotoxic metabolites from a Leptosphaeria species. Structure determination and conformational analysis

Abstract New cytotoxic epipolysulfanyldioxopiperazine dimers, leptosins K (4), K1 (5) and K2 (6), have been isolated from a strain of Leptosphaeria sp. originally isolated from the marine alga Sargassum tortile. Their stereostructures, with a different configuration from that of leptosins A-C, have been elucidated by spectral and X-ray analyses and some chemical transformations. X-Ray and NMR and NOE spectral analyses of 4 revealed that it exists in a mixture of four conformers, of which two each closely resemble, in a single crystal, and in a single conformer in solution. NOE experiments of 5 and 6 demonstrated that they exist in a mixture of two conformers slowly exchanging in CDCl3.

Gymnasterones, novel cytotoxic metabolites produced by a fungal strain from a sponge

Abstract Gymnastatins A-C, produced by a strain of Gymnasella dankaliensis from the sponge Halichondria japonica , are novel compounds with significant cytotoxicity against tumour cells in culture. Their stereostructures have been established on the basis of spectral analyses.

Leptosins M–N1, cytotoxic metabolites from a Leptosphaeria species separated from a marine alga. Structure determination and biological activities

Abstract Leptosins M ( 4 ), M1 ( 5 ) N ( 6 ) and N1 ( 7 ) have been isolated from a strain of Leptosphaeria sp. originally separated from the marine alga Sargassum tortile. Their absolute stereostructures have been elucidated by spectral analyses and some chemical transformations. Their NMR and NOE spectral analyses revealed that 4–7 exist in a single conformer of B type in acetone-d6. All the compounds exhibited significant cytotoxicity against cultured P388 cells. In addition, leptosin M ( 4 ) proved to exhibit significant cytotoxicity against human cancer cell lines, and to inhibit specifically two protein kinases, PTK and CaMKIII, and human topoisomerase II.

Penostatins, novel cytotoxic metabolites from a Penicillium species separated from a green alga

Abstract Penostatins A ( 1 ), B ( 2 ), C ( 3 ) and ( D ) have been isolated from a strain of Penicillium sp. originally separated from the marine alga Enteromorpha intestinalis , and their stereostructures have been established on the basis of spectral analyses. The compounds 1∼3 exhibited significant cytotoxicity against cultured P388 cells.

Peribysins A–D, potent cell-adhesion inhibitors from a sea hare-derived culture of Periconia species

Peribysins A-D 1-4, including a new type of furanofuran, have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai, and their relative stereostructures have been elucidated on the basis of NMR spectral analyses. All these metabolites potently inhibited the adhesion of human-leukemia HL-60 cells to HUVEC. The activity of compound 4, exhibiting the most potent inhibitory activity, was 380 times as potent as herbimycin A (standard).

Different inhibitory response of cyanidin and methylene blue for filament formation of tau microtubule-binding domain.

One of the priorities in Alzheimer research is to develop a compound that inhibits the filament formation of tau protein. Since the three- or four-repeat microtubule-binding domain (MBD) in tau protein plays an essential role in filament formation, the inhibitory behavior of cyanidin (Cy) and methylene blue (MB) with respect to heparin-induced filament formation of MBD in a neutral solution (pH 7.6) was characterized by fluorescence, circular dichroism, and electron microscopy measurements. The planar aromatic ring of Cy and the N-unsubstituted phenothiazine ring of MB were shown to be necessary for the inhibition. However, the inhibitory responses with respect to heparin-induced filament formation to the second and third repeat peptides of MBD were different: Cy suppresses the formation and MB does not prevent the formation. This suggests the importance of the first and fourth repeat peptides in the inhibitory activity of MB for MBD filament formation. In this study, we showed that the decrease of thioflavin S fluorescence intensity is not always linked to inhibition of filament formation.

Absolute stereostructures of novel cytotoxic metabolites, penostatins A–E, from a Penicillium species separated from an Enteromorpha alga

Abstract Penostatins A – E have been isolated from a strain of Penicillium sp. originally separated from the marine alga Enteromorpha intestinalis , and their absolute stereostructures and conformations have been established on the basis of spectral analyses and some chemical transformations. All the compounds except for penostatin D exhibited significant cytotoxicity against cultured P388 cells.

Pericosines, antitumour metabolites from the sea hare-derived fungus Periconia byssoides. Structures and biological activities

Pericosines A-E 1-5 have been isolated from a strain of Periconia byssoides originally separated from the sea hare Aplysia kurodai. Among them, pericosines C 3 and E 5 were separated as enantiomeric mixtures. Their stereostructures, except for compound 1, have been elucidated or identified on the basis of spectroscopic analyses, including 1D and 2D NMR techniques, and X-ray analysis. In addition, conformation for all the compounds has been discussed. Compounds 1-3 exhibited significant growth inhibition against tumour cell lines. Pericosine A 1 also showed significant in vivo tumour inhibitory activity. In addition, compound inhibited the protein kinase EGFR and topoisomerase II.