13C-n.m.r. structural study on an enteric pharmaceutical coating cellulose derivative having ether and ester substituents.
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Biomedical subjects
Publications and source records attributed to Y Tezuka.
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18 beta-Glycyrrhetic acid (GA, an aglycone of glycyrrhizin) is converted to 3-oxo-18 beta-glycyrrhetic acid (3-oxoGA) in the presence of NADP+ by rat liver homogenates, but GA was converted in the presence of NADPH to two other metabolites showing lower Rf values on thin-layer chromatography (TLC) than those of GA and 3-oxoGA by postmitochondrial supernatant of rat liver. The GA-metabolizing activity in the presence of NADPH was localized in microsomes, similar to localization of GA-oxidizing activity to 3-oxoGA. The GA-metabolizing activity required NADPH as a cofactor and O2 for full activity and was inhibited with CO, suggesting the hydroxylation reaction of GA by cytochrome P450. Two metabolites (I and II, lower and higher Rf values on TLC, respectively) were purified on preparative TLC. Mass spectral (MS) analyses of II and methyl ester of acetylated I indicated the formation of monohydroxylated metabolites. On the basis of 3H- and 13C-NMR assignments I and II were identified to be 22 alpha- and 24-hydroxy-18 beta-glycyrrhetic acids, respectively. 3-OxoGA and 3-epi-18 beta-glycyrrhetic acid (3-epiGA) seem to be also hydroxylated at C-22 and C-24. A metabolite of 3-oxoGA showing a lower Rf value was also identified as 22 alpha-hydroxy-3-oxo-18 beta-glycyrrhetic acid by MS and 3H- and 13C-NMR spectral analyses. In 22 alpha-hydroxylation the best substrate was 3-oxoGA, followed by GA and 3-epiGA. On the other hand, for 24-hydroxylation the best substrate was GA, then 3-oxoGA, and 3-epiGA in order. However, 18 alpha-glycyrrhetic acid (18 alpha-GA) was a poor substrate for both 22 alpha- and 24-hydroxylation.
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The structure of scopadulcic acid B (2, SDB), a major ingredient of the Paraguayan herb "Typychá kuratũ" (Scoparia dulcis L.), was elucidated mainly by comparison of its spectral data with that of scopadulcic acid A (1). SDB inhibited both the K(+)-dependent adenosine triphosphatase (ATPase) activity of a hog gastric proton pump (H+, K(+)-ATPase) with a value of 20-30 microM for IC50 and proton transport into gastric vesicles. Pharmacokinetic studies of SDB in rats indicated that plasma SDB concentrations after i.v. injection of the sodium salt of SDB (SDB-Na) were described reasonably well by a two-compartment open model with Michaelis-Menten elimination kinetics. Plasma concentrations after oral administration of SDB-Na or SDB showed a much slower decline than what was expected following the i. v. study. It was suggested that the sustained plasma level of SDB after oral administration of SDB-Na or SDB was accounted for by relatively slow but efficient gastro-intestinal absorption in rats.
A new gamma-lactone derivative named davallialactone (4) and the 7-O-beta-D-glucuronide of (+/-)-eriodictyol (5a) have been isolated from Davallia mariessi Moore along with caffeic acid (1), 4-beta-D-glucopyranosylcaffeic acid (2) and 4-O-beta-D-glucopyranosyl-p-coumaric acid (3). The structures of the new compounds were determined by chemical and spectroscopic methods including two-dimensional nuclear magnetic resonance (2D NMR) techniques, especially 1H-detected heteronuclear multiple-bond multiple-quantum coherence and long-range C-H J-resolved 2D NMR techniques.
Two new phloroglucinol derivatives, isomallotolerin (1) and isomallotochromanol (2), were isolated from the cytotoxic fraction of the pericarps of Mallotus japonicus. The new derivatives were identified as 3-(3-methyl-2-hydroxybut-3-enyl)-5-(3-acetyl-2,4-dihydroxy-5-methy l-6- methoxybenzyl)-phlorisobutyrophenone (1) and 6-acetyl-5,7-dihydroxy-8-(3-acetyl-2,4-dihydroxy-5-methyl-6-methoxybenzy l)-2,2- dimethyl-3-hydroxychroman (2) from chemical and spectral data. Isomallotolerin and its acetate were found to be cytotoxic to KB cell line.
The structure of a new minor saponin isolated from the leaves of Panax ginseng C. A. Meyer was elucidated on the basis of chemical evidences and spectral data. The saponin was named as ginsenoside-La.
Six compounds were isolated from the root of Astragalus chrysopterus Bunge. One of them was identified as a new triterpenoid glycoside, named astrachrysoside A. Its structure was elucidated as 3-O-[alpha-L-rhamnopyranosyl (1----2) beta-D-xylopyranosyl]-cycloastragenol on the basis of physicochemical evidence and chemical reactions. The others were shown to be known compounds, astrasieversianin XV (II), 7,2'-dihydroxy-3',4'-dimethoxy-isoflavane-7-O-beta-D-glucoside (III), soyasaponin I, daucosterol and beta-sitosterol. Full assignment of the chemical shift signals of II and III were established by various 2D-NMR techniques.
The predominant bacterium of activated sludge classified as belonging to the genus Flavobacterium showed good flocculent growth in the presence of both calcium and magnesium ions, although capsular material or gelatinous matrix was not detectable in the flocs. The bacterium accumulated a large amount of poly-beta-hydroxybutyrate when grown on glucose, but not on peptone, in spite of good flocculent growth on both substrates. When the flocs formed during growth phase were suspended in deionized water and shaken for a few minutes, they disintegrated perfectly, and a uniformly dispersed cell suspension was obtained. Furthermore, when the dispersed cell suspension thus obtained was added with each of various mineral salts and shaken for a few minutes, the cells flocculated again, the resultant supernatant solution being almost clear. Even if the dispersed cells were killed by heat or treated by trypsin, they did not lose the ability to form flocs when added with mineral salts. Since the electric charge of the cell surface was negative, a possible mechanism of floc formation was suggested as follows: negatively charged surfaces of adjacent cells are bridged by ionic bonds intermediated by cations. The bacterium utilized a relatively wide variety of organic compounds and showed high metabolic activity comparable to that of naturally activated sludge. These properties, along with floc-forming ability, were considered to be factors for making the bacterium predominant in activated sludge.
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The composition of propolis, a resinous hive product collected by honeybees from various plant sources, depends on various factors such as season and vegetation of the area. Based on standards (either isolated from Brazilian propolis or reported from propolis) including chromane, diterpenes and phenolic compounds, different Brazilian propolis were analysed by LC-MS in order to determine their chemical constituents. Dicaffeoylquinic acids were detected in almost all water extracts of Brazilian propolis, whereas diterpenes, flavonoids and prenylated phenolic compounds were found in their methanol extracts. Based on the identified chemical constituents and their biological activities, it was determined that the quality of Brazilian propolis could be directly related to the phenolic constituents. Moreover, Baccharis dracunculifolia was concluded to be an important source of Brazilian propolis. Propolis samples from Peru, China and the Netherlands were also studied.
Two new cytotoxic chromene derivatives, butyrylmallotochromene [10] and isobutyrylmallotochromene [11], were isolated from the pericarps of Mallotus japonicus. The new derivatives were identified as 5,7-dihydroxy-6-(2',4'-dihydroxy-3'-acetyl-5'-methyl-6'-methoxybenzyl)-8 - butyryl-2,2-dimethylchromene [10] and 5,7-dihydroxy-6-(2',4'-dihydroxy-3'-acetyl-5'-methyl-6'-methoxybenzyl)-8 - isobutyryl-2,2-dimethylchromene [11] by means of spectral data. These compounds and their respective acetylation and methylation products were found to be cytotoxic against KB cell lines.
Primary tissue failure of bioprosthetic heart valves refers primarily to calcification of the leaflets of the bioprosthesis. A 75 year old patient underwent reoperation 15 years after mitral valve replacement with a Carpentier-Edwards porcine bioprosthesis. The extracted bioprosthetic valve was found to have one prolapsed leaflet and a small amount of calcification on all three leaflets without tear or perforation. The two commissures suspending the prolapsed leaflet were detached, causing mitral valve regurgitation.