Biomedical subjects
Publications and source records attributed to Akiyo Sakushima.
A modified procedure for determining absolute configurations using an induced CD method and molecular mechanics calculations is disclosed. The practical usefulness of the present technique was demonstrated by its application to a few natural products.
We recently isolated 4-nitrophenol, 2-methyl-4-nitrophenol, 3-methyl-4-nitrophenol, and 4-nitro-3-phenylphenol from diesel exhaust particles (DEP) and identified them as vasodilators. Because these compounds are alkylphenolic derivatives that might mimic hormones, we evaluated their estrogenic activity by human estrogen receptor (hER)-yeast screen assay. All of these nitrophenol derivatives except 2-methyl-4-nitrophenol exhibited estrogenic activity. Some estrogenic compounds are also anti-androgenic, so we measured the anti-androgenic activity of the same compounds by human androgen receptor (hAR)-yeast screen assay. We found anti-androgenicity in all four nitrophenols. Nitrophenols in DEP possess not only vasodilatory activity but also estrogenic and anti-androgenic activity.
In our continuing studies on estrogenic compounds in diesel exhaust particles (DEP), we have reported the systematic separation of alkyldibenzothiophenes from the estrogenic hexane fraction of DEP. In this study, another estrogenic fraction was further isolated and characterized. DEP were roughly fractionated by successive extraction with hexane, benzene, dichloromethane, methanol, 1 M ammonia and 1 M HCl. The hexane extract, which exhibited estrogenic activity, was further fractionated by column chromatography and high performance liquid chromatography (HPLC). From one of the obtained fractions that showed estrogenic activity, three alkyltrimethylbenzenes were identified by gas chromatography-mass spectrometry (GC-MS) and 1H-nuclear magnetic resonance (NMR) spectroscopy.
The compounds in diesel exhaust particles (DEP) that are responsible for vasodilatation were isolated and characterized for the first time. From benzene extract of DEP, 2-methyl-4-nitrophenol, 3-methyl-4-nitrophenl and 4-nitrophenol were isolated, and their vasodilatation activities were confirmed. 3-methyl-4-nitrophenol caused dilatation of rat thoracic artery, and the other two nitrophenols, also showed vasodilatation activities.
In an earlier study using a recombinant yeast screen we found that a suspension of diesel exhaust particles (DEP) and some extracts of DEP are not estrogenic but possess anti-estrogenic activity. In the present study, estrogenic and anti-estrogenic activities of two types of DEP, type-1 (old type) and type-2 (new type) were compared. Whole DEP of both types were found to possess estrogenic and anti-estrogenic activities. The DEP were serially extracted with organic solvents and then with 1 M ammonia and 1 M HCl. In type-2 DEP, the ratio of dry weight of a hexane extract was higher than those of methanol and ammonia extracts, which were lower than those in type-1 DEP. In the hexane extract, estrogenic activity was found in both types of DEP. In the benzene and dichloromethane extracts, estrogenic and anti-estrogenic activities were found in both types of DEP. In the methanol extract, estrogenic activity was found in type-2 DEP, and extracts of both types decreased the activity of estrogen. Anti-estrogenic activity was found in extracts of ammonia and HCl from both types of DEP. It was found that both type-1 and type-2 DEP possess estrogenic and anti-estrogenic activities.
Taxifolin 3-O-glucoside isomers, [(2R, 3R)-, (2R, 3S)-, (2S, 3R)- and (2S, 3S)-] were isolated from leaves of Chamaecyparis obtuse (Cupressaceae). Their structures were elucidated on the basis of UV, MS, CD, 1H- and 13C-NMR spectral data, including 2D shift correlation. It was found that the compounds could be distinguished by the use of 1H- and 13C-NMR spectral data.
In a previous study, we focused on estrogenic activity of the hexane extract of diesel exhaust particles (DEP). The extract of hexane was first fractionated to acidic, phenolic and neutral portions according to their chemical properties, of which the neutral fraction was fractionated by column chromatography on silica gel. The chemical structures of compounds in these fractions were then analyzed. It was found that the neutral fraction of the hexane extract of DEP contains dibenzothiophene derivatives, one of which, 4,6-dimethyldibenzothiophene, possesses estrogenic activity.
The threo and erythro forms of guaiacylglycerol-7'-O-methyl 8'-vanillic acid ethers, threo and erythro guaiacylglycerol 8'-vanillin ethers, and threo guaiacylglycerol 8'-(4-hydroxymethyl-2-methoxyphenyl) ether have been isolated from fruits of Boreava orientalis. Structural determinations were made on the basis of UV, MS, 1H- and 13C-NMR spectral data, including two-dimensional shift correlation. The relative configurations were assigned on the basis of 1H-NMR chemical shifts.
(2S, 3S)-Taxifolin 3-O-arabinoside, a new dihydroflavonol glycoside, together with the known substances, (2R 3R)-taxifolin 3-O-arabinoside, astragalin, isoquercitrin, and cosmosiin, were isolated from the leaves of Trachelospermum jasminoides var. pubescens. Structural elucidation was carried out by spectroscopic methods, and the absolute configurations of C-2 and C-3 in taxifolin 3-O-arabinosides were determined on the basis of circular dichroism. Unlike the dihydroflavonol glycosides, (2R 3R)-taxifolin 3-O-glucoside and (2R, 3R-taxifolin 3-O-arabinoside, the novel (2S, 3S)-taxifolin 3-O-arabinoside is not effective as a zoospore attractant of the plant pathogenic fungus Aphanomyces cochlioides.