Taro Amagata

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.

Gymnastatins and Dankastatins, Growth Inhibitory Metabolites of a Gymnascella Species from a Halichondria Sponge

Four new metabolites, gymnastatins Q ( 3) and R ( 4) and dankastatins A ( 5) and B ( 6), have been isolated from the mycelial MeOH extract of a fungal strain of Gymnascella dankaliensis separated from a Halichondria sponge. Their stereostructures have been established on the basis of spectroscopic analysis using 1D and 2D NMR techniques. All of the isolated metabolites ( 3- 6) exhibited growth inhibition against the P388 cancer cell line. Furthermore, gymnastatin Q ( 3) showed appreciable growth inhibition against BSY-1 (breast) and MKN7 (stomach) human cancer cell lines.

First total syntheses and configurational assignments of cytotoxic trichodenones A–C

Abstract Total syntheses of cytotoxic trichodenones A–C, produced by a strain of Trichoderma harzianum from the sponge Halichondria okadai, have been achieved, and the natural trichodenones B and C have been established to have (4R,1′R)- and (1′R)-configurations, respectively. From this synthesis and chiral HPLC analysis, it was deduced that the major molecule with R-configuration coexists with its enantiomer in natural trichodenone A.

Dankasterone, a new class of cytotoxic steroid produced by a Gymnascella species from a marine sponge

Dankasterone, produced by a strain of Gymnascella dankaliensis from the marine sponge Halichondria japonica, is a novel class of steroid with significant cytotoxicity against tumour cells in culture.

Absolute stereostructures of novel cytotoxic metabolites, gymnastatins A–E, from a Gymnascella species separated from a Halichondria sponge

Gymnastatins A–E have been isolated from a strain of Gymnascella dankaliensis originally separated from the sponge Halichondria japonica, and their absolute stereostructures have been established on the basis of spectroscopic analyses using 1D and 2D NMR techniques and some chemical transformations. Among them gymnastatins A–C exhibited significant cytotoxicity against cultured P388 cells.

Creation of an HDAC-Based Yeast Screening Method for Evaluation of Marine-Derived Actinomycetes: Discovery of Streptosetin A

A histone deacetylase (HDAC)-based yeast assay employing a URA3 reporter gene was applied as a primary screen to evaluate a marine-derived actinomycete extract library and identify human class III HDAC (SIRT) inhibitors. On the basis of the bioassay-guided purification, a new compound designated as streptosetin A (1) was obtained from one of the active strains identified through the yeast assay. The gross structure of the new compound was elucidated from the 1D and 2D NMR data. The absolute stereostructure of 1 was determined based on X-ray crystal structure analysis and simulation of ECD spectra using time-dependent density functional theory calculations. This compound showed weak inhibitory activity against yeast Sir2p and human SIRT1 and SIRT2.

The unexpected isolation of CTP-431, a novel thiopyrone from the sponge Cacospongia mycofijiensis.

A reinvestigation of a Fijian collection of Cacospongia mycofijiensis has yielded the known mycothiazole and a novel heterocyclic, CTP-431 (1). Its structure including absolute configuration as 8R,9R,10S,13S was established using NMR data, calculated DFT (13)C chemical shifts and results from X-ray crystallography. It is possible that the tricyclic skeleton of CTP-431 (1) is biosynthetically related to the macrolide latrunculin A, however the thiopyrone moiety of 1 has no previous precedent in natural products chemistry.

Gymnastatins I-K, cancer cell growth inhibitors from a sponge-derived Gymnascella dankaliensis

The Halichondria sponge-derived fungus, Gymnascella dankaliensis, was cultured in a malt extract medium containing the bromine source. Three new metabolites, gymnastatins I (5)-K (7), have been isolated from the mycelial MeOH extract. The spectroscopic analyses using 1D and 2D NMR techniques have established the stereostructures of 5-7 in which chlorine atoms in gymnastatins A (1)-C (3) are respectively replaced by bromine atoms. All of the isolated metabolites (5-7) exhibited growth inhibition against the P388 cancer cell line. Furthermore, gymnastatins I (5) and J (6) showed appreciable growth inhibition against the human cancer cell lines.

Missasigned Structures: Case Examples from the Past Decade

Research on marine-derived biosynthetic products is continuing on a worldwide basis, resulting in an annual rise in the number of increasingly complex marine natural products reported in the literature. However, corresponding to the increase in the number of published marine-derived structures is a concurrent rise in the number of disputed and revised structures. This chapter begins by introducing the concept of structural diversity. Next, many of the common problems encountered in the process of marine natural product structure elucidation are discussed.

Evaluation of benzoic acid derivatives as sirtuin inhibitors.

Employing a genetically modified yeast strain as a screening tool, 4-dimethylaminobenzoic acid (5) was isolated from the marine sediment-derived Streptomyces sp. CP27-53 as a weak yeast sirtuin (Sir2p) inhibitor. Using this compound as a scaffold, a series of disubstituted benzene derivatives were evaluated to elucidate the structure activity relationships for Sir2p inhibition. The results suggested that 4-alkyl or 4-alkylaminobenzoic acid is the key structure motif for Sir2p inhibitory activity. The most potent Sir2p inhibitor, 4-tert-butylbenzoic acid (20), among the tested compounds in this study turned out to be a weak but selective SIRT1 inhibitor. The calculated binding free energies between the selected compounds and the catalytic domain of SIRT1 were well correlated to their measured SIRT1 inhibitory activities.