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Volume 37, Issue 9
Displaying 1-50 of 73 articles from this issue
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Matsue EBITANI, Hiroshi KASHIWAGI, Masami INOUE, Sburo ENOMOTO, Toshim ...1989 Volume 37 Issue 9 Pages 2273-2275
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe X-ray diffraction patterns of two polymorphic forms of riboflavin tetrabutyrate (RTB) powders were examined. The orange powder showed sharp peaks suggesting a well-crystallized material, while the yellow powder showed broad peaks suggesting a polymer-like material. By using the cell constants of RTB crystal, all peaks in the Debye-Sheller powder patterns of RTB were assigned. Increase of the ratio of H2O in the recrystallization solvent (MeOH-H2O) decreased the peak intensities of X-ray patterns corresponding to specific faces of RTB crystals, reflecting the direction of growth of RTB crystals in the presence of H2O.View full abstractDownload PDF (488K) -
Yoshiro OHMOMO, Shin'ichiro OKUYAMA, Yasuhiro MAGATA, Yoko UENO, Chiak ...1989 Volume 37 Issue 9 Pages 2276-2281
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe usefulness of radioiodination via demetallation of aryltrimethylsilanes was demonstrated. The radioiodination reaction was found to be very rapid and the regiospecific incorporation of radioiodine could be carried out with high radiochemical yields and high radiospecific activity. 125I-Labeled dimethylaminoethyl iodophenoxyacetate derivatives (5a-e), dimethylaminoethyl iodophenoxyacetamide derivatives (7a-c), iodophenoxyethyl ethylenediamine derivatives (9, 14) and an iodophenoxyethylpiperazine derivative (18) were efficiently synthesized from the corresponding aryltrimethylsilyl intermediates (4a-e, 6a-c, 8, 13, 17) by this method.View full abstractDownload PDF (802K) -
Yoshiro OHMOMO, Shin'ichiro OKUYAMA, Yasuhiro MAGATA, Yoko UENO, Chiak ...1989 Volume 37 Issue 9 Pages 2282-2286
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The α, α-dimethylester derivative (1e), amide derivatives (2a-c) and diamine derivatives (3a, b, 4), which were stable to hydrolysis, showed low blood activity levels following i.v. administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be useful as potential brain imaging radiopharmaceuticals with SPECT devices.View full abstractDownload PDF (716K) -
Jun-ichi YAMASHITA, Hiroshi MATSUMOTO, Kazuhiro KOBAYASHI, Kazuharu NO ...1989 Volume 37 Issue 9 Pages 2287-2292
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA practical synthesis of 3'-O-benzyl-2'-deoxy-5-trifluoromethyluridine (1), a candidate antitumor agent for clinical testing, was developed from 2'-deoxy-5-iodouridine (3). Benzylation of 2'-deoxy-5-iodo-5'-O-trityluridine (14) with benzyl bromide and sodium hydride in tetrahydrofuran gave the 3'-O-derivative (16). Benzoylation of 16 afforded the N3-benzoyl derivative (17). Coupling of 17 with trifluoromethylcopper, prepared from bromotrifluoromethane and copper powder in the presence of 4-dimethylaminopyridine, gave the 5-trifluoromethyl derivative (19) minimally contaminated with the 5-pentafluoroethyl compound. Deprotection of 19 furnished 1.View full abstractDownload PDF (1013K) -
Jean Claude TEULADE, Alain GUEIFFIER, Jean Pirre CHAPAT, Gerard GRASSY ...1989 Volume 37 Issue 9 Pages 2293-2297
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS3-Nitroso-2(2-nitrophenyl)imidazo[1, 2-α]pyridine was converted to its diamino derivative (5) and the open-chain compound 2-N(2-pyridyl)benzimidoyl cyanide (6). Compound 5 was condensed with triethyl orthoformate or 2-chlorobenzaldehyde to afford the pyrido[1', 2' : 1, 2]imidazo[5, 4-d][1.3]benzodiazepines (7a, b). X-Ray crystallographic analysis confirmed the structure of 7a. The structure of 7b was assigned by two-dimensional nuclear magnetic resonance techniques, 1H-1H and 13C-1H correlatino spectroscopy.View full abstractDownload PDF (738K) -
Hiromitsu SAITO, Fumio SUZUKI, Tadashi HIRATA1989 Volume 37 Issue 9 Pages 2298-2302
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSVarious kinds of 1, 2-disubstituted-1-carbacephems were synthesized by employing several electrophilic reactions (e.g. oxidation, halogenation, halogenohydrination) toward the aldehyde 2 followed by cyclization, and also from 1, 2-dehydro-1-carbacephem 10. The stereochemistry of the 1, 2-disubstituted-1-carbacephems prepared was determined by proton nuclear magnetic resonance (1H-NMR) analysis. The diol 4a, chlorohydrin 15a and bromohydrin 17a were converted to the corresponding 7-N-acylated compounds 27a-c. Antibacterial activities of 27a-c, however, were rather low compared with those of KT 3919 (non-substituted carbocephem) and KT 3933 (2α-hydroxy carbacephem), which are the racemates of KT 3767 and KT 3937, respctively.View full abstractDownload PDF (826K) -
Hideaki SASAKI, Kenji KAWANISI, Tokujiro KITAGAWA, Tetsuro SHINGU1989 Volume 37 Issue 9 Pages 2303-2306
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe title compound (6) was synthesized by the one-pot coupling reaction of 1, 3-bis(2-isocyano-2-tosylethyl)benzene (4) with thiophene-2, 5-dicarbaldehyde (5), along with the higher homolog (7). On the basis of proton nuclear magnetic resonance (1H-NMR) spectra at various temperatures, it was considered that (i) the conformational change of 6 at room temperature was strongly erstricted because of the observation of very broad signals in both aromatic and aliphatic regions, (ii) the coalescence temperature (TC) of the methylene proton signals is 69°C and the energy barrier (ΔG〓) of the conformational change is calculated to be 69.4kJ/mol, which is higher than those of the dioxazolo[32]-metacyclophane (1a) and dioxazolo[32](2, 5)furanometacycophane (3), and (iii) at -31°C, 6 exists in two fixed conformers, i.e., syn and anti forms because of the observation of a set of the oxazole C2-H signals. These results suggest that the rigidity of the thiophene-containign heterophane 6 is due to the bulkiness of the large sulfur atom as well as the presence of a longer carbon-sulfur bond.View full abstractDownload PDF (519K) -
Takeshi KAWAMATA, Kenzo HARIMAYA, Yoichi IITAKA, Seiichi INAYAMA1989 Volume 37 Issue 9 Pages 2307-2309
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe Diels-Alder reaction of 3-acetoxy-1-vinylcyclohexene (1c) with methyl vinyl ketone (MVK) at 110 and 150°C gave predominantly the adducts 1-acetoxy-8-acetyl-8aβH-4a(5)-octalin, 3b (8βH) and 3a (8αH), respectively, along with other minor adducts. The stereochemistry of 3a was independently confirmed by X-ray crystallographic analysis of the p-bromobenzoate (3e) derived from 1-desacetyl-3a(3d). The predominant approach of the dienophile (MVK) to 1c was found to have occurred anti to the allylic acetate group, contrary to the empirical rule proposed recently.View full abstractDownload PDF (651K) -
Yueh-Hsiung KUO, Sheng-Tsair LIN, Rong-En WU1989 Volume 37 Issue 9 Pages 2310-2312
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe following constituents were isolated from the nutmeg of Myristica cagayanesis MERR. : trimyristin (1), otobain (2a), malabaricone A (3), otobanone (2b), cagayanin (4a), and cagayanone (4b). Compounds 2b, 4a and 4b are new lignans, and their structures were determined from spectral and chemical evidence.View full abstractDownload PDF (626K) -
Yasutoshi KAWASE, Makoto KOIZUMI, Shigenori IWAI, Eiko OHTSUKA1989 Volume 37 Issue 9 Pages 2313-2317
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSHexaribonucleotides containing inosine at a pairing position adjacent to the other four major nucleosides (GGINCC, N=A, C, G, U) were synthesized in solution by the phosphotriester method using 2'-O-tetrahydrofuranyl protecting groups. 5'-O-Dimethoxytrityl-2'-O-tetrahydropyranylinosine 3'-O-(metyl-N, N-diisopropyl)phosphor-amidite was used for solid-phase syntheses of decaribonucleotides (CGNGAUCICG, N=A, C, G, U). Thermal stabilities and circular dichroism spectra for these self-complementary duplexes were measured. The stabilizing effects of wobble base pairs in these duplexes were estimated as IC>IA>IU>IG.View full abstractDownload PDF (785K) -
Hideaki KAWAI, Miciko NISHIDA, Yukiko TASHIRO, Masanori KUROYANAGI, Ak ...1989 Volume 37 Issue 9 Pages 2318-2321
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSSix new triterpenoid saponins, named udosaponins A, B, C, D, E, and F, were isolated as methyl esters, 2, 6, 7, 8, 9 and 11, respectively, along with five kinown saponins as methyl esters, 1, 3, 4, 5 and 10, from the aerial parts of Aralia cordata THUNB. (Araliaceae). On the basis of 13C-nuclear magnetic resonance spectra and chemical evidence, these saponins were established to be oleanane-type saponins having a glucuronopyranosyl residue at the C-3 position of oleanolic acid and hederagenin.View full abstractDownload PDF (604K) -
Yoshio OKADA, Yutaka MATSUNO, Yasuhiro NSHIYAMA, Yuko TSUDA, Shin IGUC ...1989 Volume 37 Issue 9 Pages 2322-2329
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA pentacosapeptide corresponding to the entire amino acid sequence of Neurospora crassa metallothionein and several related cysteine-containing peptides were synthesized by the conventional solution method and their heavy metal-binding properties were examined. The Cu2+-or Cu+-binding properties of the various peptides were similar to each other, whereas the Cd2+-binding properties of these peptides were fairly structure dependent.View full abstractDownload PDF (1147K) -
Akito NAKAMURA, Shin-ichi NAGAI, Taisei UEDA, Jinsaku SAKAKIBARA, Yosh ...1989 Volume 37 Issue 9 Pages 2330-2333
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA technique to assay Na+ ions in cells is presented. Intracellular and extracellular Na+ ions in a suspension of guinea pig erythrocytes were conveniently determined by using sodium-23 unclear magnetic resonance (23Na-NMR), in combination with two anionic shift reagents : Dy(TTHA)3- and Dy(PPPi)27-. Monensin (1), monensylalanine (2b), monensylserine (2c), and monensylphenylalanine (2d) induced large increases of intracellular Na+ ion concentration ([Nain]), while monensylglycine (2a), monensyltyrosine (2e), monensylaspartic acid (2f), and monensylglutamic acid (2g) showed slight increases. The values of initial increasing rate (Vi) of 2a-g were much smaller than that of 1. This fact was probably due to the lower lipophilicity of 2a-g than 1, because a good correlation was observed between Vi and Rm50 values of 1 and 2a-g. This lower lipophilicity is a consequence of conformational differences between 1 and 2a-g.View full abstractDownload PDF (621K) -
Kazuyoshi TAKEDA, Kanoko TSUBOYAMA, Hiroaki TAKAYANAGI, Rie SHIROKAMI, ...1989 Volume 37 Issue 9 Pages 2334-2337
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSS, S'-Bis(1-phenyl-1H-tetrazol-5-yl) dithiocarbonate (1) was synthesized in good yield from 1-phenyl-5-mercapto-5H-tetrazole (2) and trichloromethyl chloroformate (TCF). THe structure of 1 was confirmed by using X-ray crystal analysis. The reagent (1) could be applied to the formatio of amides, Friedel-Crafts type reactions, isothiocyanate syntheses, and carbonyl group insertion reactions.View full abstractDownload PDF (657K) -
Jun-ichi HARUTA, Koichi NISHI, Kazumi KIKUCHI, Satoshi MATSUDA, Yasumi ...1989 Volume 37 Issue 9 Pages 2338-2343
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe key intermediate in the synthesis of 1β-methylcarbapenem, (3S, 4R)-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-4-[(1S)-1-methyl-2-propynyl]-2-azetidinone (5β), was prepared by propargylation of (3R, 4R)-4-acetoxy-3-[(1R)-1-(tert-butyldimethylsilyloxy)ethyl]-2-azetidinone (3) with 3-methyl-1-tributylstannylallene (4) in the presence of a Lewis acid and successfully converted to a novel 2-(heteroarylthiomethyl)-1β-methylcarbapenem (2).View full abstractDownload PDF (925K) -
Yoshisuke TSUDA, Makiko HANAJIMA, Naohisa MATSUHIRA, Yukihiro OKUNO, K ...1989 Volume 37 Issue 9 Pages 2344-2350
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSMost of the glycosides examined were smoothly oxidized by the bis-tributyltin oxide-bromine method without protection of the other hydroxyl groups to the mono-oxo derivatives in high yield and with high regioselectivity. The regioselectivity (position of oxidation) can be predicted from two independent rules : anomeric control (the oxidation takes place at C-3 for the glycosides which have an equatorial glycosidic linkage and at C-4 for those which have an axial glycosidic linkage) and axial oxidation for cis-1, 2 glycols.View full abstractDownload PDF (1028K) -
Chung-Fang LAI, Kazunori ODASHIMA, Kenji KOGA1989 Volume 37 Issue 9 Pages 2351-2354
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSNovel water-soluble bis-cyclophanes (3a-c) with quaternary ammonium nitrigens, composed of two untis of QCP44 (2) connected by appropriate bridges, were synthesized as hosts having two discrete hydrophobic cavities to bind two guest molecules simultaneously or a single guest molecule via double recognition in neutral water. Glutaryl, terephthaloyl and isophthaloyl groups were used as spacers to bridge the two cyclophane units. THe bridge formation was carried out using 5 as an intermediate, in which three of the four nitrogens of CP44 (1) were protected. The details of the synthesis and characterization of duplex hosts (3a-c) as well as of the reference compounds (9-11) are described.View full abstractDownload PDF (753K) -
Toshihiro FUJIOKA, Masayo IWAMOTO, Yukiko IWASE, Shizuko HACHIYAMA, Hi ...1989 Volume 37 Issue 9 Pages 2355-2360
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe structures of lobatosides B, E, F and G, the dicrotalic acid esters of bayogenin bisdesmosides isolated from the harb of Actinostemma lobatum MAXIM. (Cucurbitaceae), were determined on the basis of chemical and spectral evidence.Lobatoside B is the dicrotalic acid (3-hydroxy-3-methylglutaric acid) ester of 3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranosyl]bayogenin 28-[α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl] ester. Dicrotalic acid is linked at one end to the C6-hydroxyl group of the terminal β-D-glucopyranosyl group in the C3-linked sugar moiety, and at the other end to the C4-hydroxyl group of the α-L-rhamnopyranosyl group in the ester-linked sugar moiety to form a macrocyclic structure (cyclic bisdesmoside).Lobatosides E, F and G are cyclic bisdesmosides of bayogenin similar to lobatoside B, but different in the numbers and species of the component sugars and positions of the ester linkages of the dicrotalic acid.View full abstractDownload PDF (877K) -
Mitsuaki YODO, Hiroshi HARADA1989 Volume 37 Issue 9 Pages 2361-2368
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA method for synthesizing methyl 2, 3-dihydro-2-benzofurancarboxylates from o-allylphenols is described. The reaction of 6-allyl-2, 3-dichlorophenol (3) with benzenesulfenyl chloride (PhSCl) in acetonitrile gave a mixture of PhSCl-adducts, which was heated in aqueous acetonitrile then with sodium bicarbonate to obtain 6, 7-dichloro-2-(phenylthiomethyl)-2, 3-dihydrobenzofuran (6). α-Dichlorination of the phenylthiomethyl group of 6 and subsequent methanolysis gave the methyl ester 5 in high yield. The generality of this synthetic method was examined by the conversion of o-allylphenols 11 having various substituents on the benzene ring into the corresponding methyl esters 23. Cyclizations of 11 to the sulfides 12 could be achieved similarly to hte case of 3. However, in the subsequent conversions of 12 to 23, selective α-dichlorination followed by methanolysis could be achieved only with 12 substituted with an electron-withdrawing group such as a chloro or nitro group.View full abstractDownload PDF (1164K) -
Masao MIYAUCHI, Kunihiro SASAHARA, Koichi FUJIMOTO, Isao KAWAMOTO, Jun ...1989 Volume 37 Issue 9 Pages 2369-2374
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.View full abstractDownload PDF (743K) -
Masao MIYAUCHI, Hideshi KURIHARA, Koichi FUJIMOTO, Isao KAWAMOTO, Juny ...1989 Volume 37 Issue 9 Pages 2375-2378
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe effect of substituents at the C-3 position on the degradation kinetics of the pivaloyloxymethyl (POM) ester of Δ3 cephalosporin in phosphate buffer solution (pH6-8) was investigated. In the degradation, the isomerization process to the Δ2 ester was the rate-determining step. In this study, the logarithm of the isomerization rate to the Δ2 ester (log k12) correlated with the carbon-13 unclear magnetic resonance chemical shift difference value at C-3 and C-4 of the Δ3 ester (Δδ(4-3)). The energy level of the lowest unoccupied molecular orbital (LUMO) of the Δ3 esters also correlated with log k12. The electronic properties at the C-2 position had no effect on the isomerization reaction. On the other hand, the logarithm of the isomerization rate back to the Δ3 ester (log k21) correlated with the van der Waals volume (MV) of the 3-substituent. These results show that the substituent at the C-3 position influences mainly the electronic structure of the conjugated π-bond system (C3=C4-C4=O) and consequently affects the feasibility of isomerization to the Δ2 ester, i.e., the stability to degradation.View full abstractDownload PDF (569K) -
Hideki MIYAZAKI, Nobuyuki OHKAWA, Norio NAKAMURA, Tomiyoshi ITOU, Tosh ...1989 Volume 37 Issue 9 Pages 2379-2390
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSSix-membered lactone and tetrahydropyran analogues of platelet-activating factor (PAF), 4-11, and related antagonistic derivatives 41-46 were synthesized. None of the δ-lactones 4-7 showed PAF-like activities, while the corresponding cyclic ethers 8, 9 and 11 were slightly active. Some of the cyclic antagonists showed more potent inhibitory activities than the open chain antagonist CV-3988 against platelet aggregation (rabbit platelet-rich plasma, IC50) and hypotension (rat, DI50) induced by C16-PAF : e.g. dl-3-{6-[O-(trans-3-heptadeclcarbamoyloxytetrahydropyran-2-yl)methyl]phosphonoxy}hexylthiazolium (inner salt)(4ld)(IC505.5×10-7M, ID500.046mg/kg, i.v.);dl-3-{5-[O-(cis-3-heptadecylcarbamoylthiotetrahydropyran-2-yl)methyl]phosphonoxy}pentylthiazolium (inner salt) (43c) (IC505.7×10-7M, ID500.076mg/kg, i.v.).View full abstractDownload PDF (1809K) -
Hideki MIYAZAKI, Norio NAKAMURA, Tomiyoshi ITO, Toshio SADA, Takeshi O ...1989 Volume 37 Issue 9 Pages 2391-2397
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSEnantiomers of platelet-activating factor (PAF) antagonists, 3-{6-[O-(trans-3-heptadecylcarbamoyloxytetrahydro-pyran-2-yl)methyl]phosphonoxy}hexylthiazolium (inner salt) (3), 3-[5-(trans-3-heptadecylcarbamoyloxytetrahydro-pyran-2-yl)methoxycarbonylamino]pentylthiazolium bromiede (4) and 3-{5-[O-(cis-3-heptadecylcarbamoylthiotetrahy-dropyran-2-yl)methyl]phosphonoxy}pentylthiazolium (inner salt) (5), were synthesized, starting from (2R, 2R)- and (2S, 2S)-tartaric acid.Antagonistic activities of these compounds against C16-PAF were measured in vitro (rabbit platelet aggregation, IC50) and in vivo (hypotension in rates, ID50). In these three enantiomeric pairs, the (3S)-(tetrahydropyran numbering) enantiomers were one order more potein than the (3R)-isomers : (2R, 3S)-3a (R-74, 654), IC50 0.59μM and ID50 0.054 mg/kg, i.v.; (2S, 3R)-3b, IC50 4.7μM and ID50 0.30 mg/kg, i.v.; (2R, 3S)-4a, IC50 0.20 μM and ID50 0.032 mg/kg, i.v.; (2S, 3R)-4b, IC50 2.2μM and IC40 0.21 mg/kg, i.v.; (2R, 3R)-5a, IC50 1.1μM and ID50 0.92 mg/kg, i.v.; (2S, 3S)-5b (R-74, 717), IC50 0.27μM and ID50 0.064 mg/kg, i.v.View full abstractDownload PDF (1097K) -
Yoshitaka OHISHI, Teruo MUKAI, Michiko NAGAHARA, Motoyuki YAJIMA, Nori ...1989 Volume 37 Issue 9 Pages 2398-2405
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSVarious benzo[b]futran derivatives with a carboxymethylsulfamoyl group were prepared and evaluated for aldose reductase-inhibitory potency. Most of the compounds displayed significant inhibitory activities (IC50, 10-8-10-7M). Among the test compounds, the compounds having a carboxymethylsulfamoyl group at the 3- or 4-position exhibited the greatest inhibitory potency. Structure-activity trends of the tested compounds are discussed.View full abstractDownload PDF (1205K) -
Hiroyoshi NOWATARI, Yasuo KURODA, Hiroshi HAYAMI, Kazuya OKAMOTO, Hisa ...1989 Volume 37 Issue 9 Pages 2406-2409
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSNovel alkyl-1, 4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and LEwis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1, 1-dicarboxylate. 1, 4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II)(five-membered ring) and 1, 3-propanediamine Pt(II)(six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1, 4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1, 1-dimethyl-1, 4-butanediamine Pt(II) complexes. In particular, 2, 2-dimethyl-1, 4-butanediamine and 2, 3-dimethyl-1, 4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1, 1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values aroung 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1, 4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.View full abstractDownload PDF (681K) -
Kazuhiro HIRABAYASHI, Susumu IWATA, Masahiko ITO, Shirou SHIGETA, Taka ...1989 Volume 37 Issue 9 Pages 2410-2412
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA sulfate (GE-3-S) prepared by chlorosulfonic acid treatment of GE-3, a partially acetylated β(1→6) glucan of the lichen Umbilicaria esculenta, inhibited the cytopathic effect of human immunodeficiency virus (HIV) and suppressed the HIV-antigen expresion in Molt-4 (clone 8) cells. GE-3-S also suppressed the giant cell formation of HIV-infected Molt-4 cells, and inhibited HIV-induced plaque formation by 50% at the dose of 19.5μg/ml and completely at 250μg/ml in MT4 cells. GE-3-S had no direct effect on the reverse transcriptase of HIV.View full abstractDownload PDF (739K) -
Phillippe HELISSEY, Sylviane GIORGI-RENAULT, Jean RENAULT, Suzanne CRO ...1989 Volume 37 Issue 9 Pages 2413-2416
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSWith the aim of obtaining new antitumor drugs more active than previously described 11H-indolo[3, 2-c]quinoline-1, 4-diones and 7, 8, 9, 10-tetrahydro-11H-indolo[3, 2-c]quinoline-1, 4-diones, the synthesis and activities of a series of 3-substituted 11H-pyrido[3', 4' : 4, 5]pyrrolo[3, 2-c]quinoline-1, 4-diones and of 7, 8, 9, 10-tetrahydro-11H-pyrido-[3', 4' : 4, 5]pyrrolo[3, 2-c]quinoline-1, 4-diones were studied. Some quinones were more cytotoxic in vitro towards L1210 leukemia cells but were not active in vivo towards murine P388 leukemia.View full abstractDownload PDF (694K) -
Tadahiro SAWAYAMA, Masatoshi TSUKAMOTO, Takashi SASAGAWA, Kazuya NISHI ...1989 Volume 37 Issue 9 Pages 2417-2422
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new series of γ-D-Glu-containing N-benzyloxycarbonyl (Z) tripeptide inhibitors of angiotensin-converting enzyme (ACE) was synthesized. The effect of varying the antepenultimate amino acid residue in this series on the biological activity was studied. Introduction of Lys and Orn residues at the P1 position provided the most potent inhibitors, 25a and 25b (IC50 : 3.5 and 4.9×10-9M, respectively), which exhibited an oral antihypertensive activity. This result suggests that basic amino acid residues at the P1 position play an important role in binding with the S1 subsite of ACE in this series. Oral antihypertensive activity of selected compounds was evaluated.View full abstractDownload PDF (850K) -
Tong Lan NGIAM, Mei Lin GO1989 Volume 37 Issue 9 Pages 2423-2426
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe anti-acetylcholinesterase activities of the ephedrine diastereomers and their N-methyl derivatives were correlated to the conformation of the molecules in solution. The stereospecificity exhibited by enantiomers of N-methyl-ψ-ephedrinc was attributed to the predominance of one preferred conformation. The possiblity of predicting the absolute configuration of chiral inhibitors from enzyme inhibitions data is discussed.View full abstractDownload PDF (617K) -
Isao KOUNO, Naosuke BABA, Miwa HASHIMOTO, Nobusuke KAWANO, Chun-Shu YA ...1989 Volume 37 Issue 9 Pages 2427-2430
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA novel sesquiterpene lactone, pseudomajucin (1) was isolated from the pericarps of Illicium majus, a Chinese Illicium plant, together with its glucoside (2). The structure elucidation of 1 was performed by the spectroscopic method, and finally by and X-ray crystallographic analysis. Interestingly, the structure of pseudomajucin resembled that of the lactone compound which was afforded by treatment of pseudoanisatin with a basic medium. The glucosidic linkage position in the structure of 2 was determined as C-7 in that of 1 by the spectroscopic analysis of 2 and its acetate.View full abstractDownload PDF (568K) -
Munehisa ARISAWA, Kazunob OHMURA, Akio KOBAYASHI, Naokata MORITA1989 Volume 37 Issue 9 Pages 2431-2434
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA cytotoxic alkylresorcinol was isolated from Lysimachia japonica THUNB. (Primulaceae) and identified as grevillol (2). t was tested for cytotoxicity against KB, B-16, PC-13, L-5178Y, P-388, and HEp-2 cells in vitro. Synthetic related compounds were also tested for cytotoxicity against the KB cell line, and the structure-activity relationships are discussed.View full abstractDownload PDF (631K) -
Adel I. EL-SEDAWY, Masao HATTORI, Kyoichi KOBASHI, Tsuneo NAMBA1989 Volume 37 Issue 9 Pages 2435-2437
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAs a part of our studies on the metabolism of cude drug components by intestinal bacteria, gentiopicroside (a secoiridoid glucoside from Gentiana lutea), was anaerobically incubated with various defined strains of human intestinal bacteria. Many species had ability to transform it to a series of metabolites. Among them, Veillonella parvula ss parvula produced five metabolites, which were identified as erythrocentaurin, gentiopicral, 5-hydroxymethylisochroman-1-one, 5-hydroxymethylisochromen-1-one and trans-5, 6-dihydro-5-hydroxymethyl-6-methyl-1H, 3H-pyrano[3, 4-c]pyran-1-one.View full abstractDownload PDF (535K) -
Yoshiyasu FUKUYAMA, Mitsuaki KODAMA, Iwao MIURA, Ziunei KINZYO, Hideo ...1989 Volume 37 Issue 9 Pages 2438-2440
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS6, 6'-Bieckol (1), 2-O-(2, 4, 6-trihydroxyphenyl)-6, 6'-bieckol (4), and 8, 8'-bieckol (2), bispolyphenols with a dibenzo-1, 4-dioxin skeleton, have been isolated as potent anti-plasmin inhibitors from the brown alga Ecklonia kurome OKAMURA. Their structures have been determined to be dimers of eckol linked at the C-6 or C-8 positions, through an aryl-aryl bond on the basis of spectral data. Their inhibitory actions on anti-plasmins (α2-macroglobulin and α2-plasmin inhibitor) and some proteases have been examined.View full abstractDownload PDF (593K) -
Susumu KITANAKA, Koreharu OGATA, Michio TAKIDO1989 Volume 37 Issue 9 Pages 2441-2444
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTwo novel C-2, 6-dideoxyglycosylflavones, torosaflavones A (1) and B (2), were isolated from the leaves of Cassia torosa CAV. The structures of the new compounds 1 and 2 were established as apigenin 6-C-β-D-olioside and diosmetin 6-C-β-D-olioside, respectively, on the basis of spectral and X-ray analysis.View full abstractDownload PDF (643K) -
Feng-E WU, Kazuo KOIKE, Taichi OHMOTO, Wei-Xin CHEN1989 Volume 37 Issue 9 Pages 2445-2447
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFrom the Chinese folk medicine "Zhu jie xian fu" (roots of Anemone raddeana REGEL, Ranunculaceae), two new oleanane-type glycosides, named reddeanosides R8 (1) and R9 (2), were isolated. The structures of 1 and 2 were determined as 3-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl oleanolic acid 28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside and 3-O-α-L-rhamnopyranosyl-(1→2)-O-β-D-glucopyranosyl-(1→2)-α-L-arabinopyranosyl 27-hydroxyolenolic acid 28-O-α-L-rhamnopyranosyl-(1→4)-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranoside, respectively.View full abstractDownload PDF (493K) -
Isao KOUNO, Naosuke BABA, Miwa HASHIMOTO, Nobusuke KAWANO, Masakatsu T ...1989 Volume 37 Issue 9 Pages 2448-2451
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThree new sesquiterpene lactones, majucin (3), neomajucin (4), and 2, 3-dehydroneomajucin (5), have been isolated from the pericarps of Chineses Illicium majus, which is a toxic plant. The spectral features of compounds 3 and 4 were similar to those of anisatin (1), a convulsant from Japanese star anise. The structure of neomajucin (4) was determined by an X-ray crystallographic analysis, and the structures of the other compounds were deduced from the 1H- and 13C-nuclear magnetic resonance spectral data, aided by an extensive analysis of the 1H-1H, 13C-1H, and 13H-1H long-range two dimensional shift-correlated spectra, on the basis of the structure of neomajucin. Only neomajucin exhibited picrotoxin-like toxicity, amounting to one-tenth of that of anisatin.View full abstractDownload PDF (615K) -
Yoshikazu FUJITA, Itsuo MORI, Kinuko IKUTA(nee FUJITA), Yoshihiro NAKA ...1989 Volume 37 Issue 9 Pages 2452-2455
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA highly sensitive spectrophotometric determination of human serum albumin (HSA) with 3', 4', 5', 6'-tetrachlorogal-lein (T.Cl.Gall)-Mo(VI) complex in a Triton X-100+polyvinyl alcohol micellar medium is proposed. This method can be used to determine up to ca. 150μg/10ml of HSA from the optical absorbance at 640nm, and is superior in sensitivity to the other extremely sensitive spectrophotometric methods. The great sensitivity of this method results from the use of third-derivative spectrophotometry. The binding parameters of T.Cl.Gall-Mo(VI) complex to HSA are n=77.3 and K=1.05×104 M-1 as determined from dual double-reciprocal plots. It is suggested that the colored complex in this system may be the association complex between [HSA]m+ and [MoVI(T.Cl.Gall)2]n- involving hydrophobic interaction between HSA and T.Cl.Gall. The proposed method should also be useful for the detection and determination of some peptides (e.g. low molecular weight peptides containing gasic amino acids), as well as proteins.View full abstractDownload PDF (601K) -
Toshiyuki OSHIMA, Kazuhiko SAGARA, Yu-Yi TONG, Guande ZHANG, Yu-Heng C ...1989 Volume 37 Issue 9 Pages 2456-2458
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new ion-pair high-performance liquid chromatographic method for the analysis of hyoscyamine and scopolamine in various kinds of crude drugs derived from solanaceous plants was evaluated using sodium dodecyl sulfate as a counter ion. A reversed-phase chromatographic system consisting of a chemically bonded ODS silica gel column with phosphate buffer (pH 2.5)-acetonitrile (65 : 35) containing 17.5mM sodium dodecyl sulfate as the mobile phase was used. Hyoscyamine and scopolamine in crude drugs derived from Scopolia, Atropa, Hyoscyamus and Datura species were separated from other compounds in the crude drugs and determined within 20 min after direct injection of the solution extracted with the mobile phase. The results for various kinds of samples are presented.View full abstractDownload PDF (556K) -
Masahiro KITO, Riichi TAWA, Shigeo TAKESHIMA, Shingo HIROSE1989 Volume 37 Issue 9 Pages 2459-2462
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA selective and sensitive assay of substrates (hypoxanthine, xanthine and allopurinol) of xanthine oxidase by reversed-phase liquid chromatography coupled with the use of immobilized enzyme reactors is described. These compounds were oxidized by immobilized xanthine oxidase and produced hydrogen peroxide, which was determined fluorometrically using immobilized peroxidase and p-hydroxyphenylacetic acid. The detection limits of hypoxanthine, xanthine and allopurinol were approximately 50, 120 and 130 pg per injection, respectively.Immobilized xanthine oxidase inhibited by oxipurinol during the assay was reactivated by 2, 6-dichlorophenolin-dophenol and could be used for a long period without a significant activity loss. These methods were applied to plasma and urine samples.View full abstractDownload PDF (585K) -
Terumichi NAKAGAWA, Kenji IZAWA, Shingemasa YAGI, Akimasa SHIBUKAWA, H ...1989 Volume 37 Issue 9 Pages 2463-2466
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSWhen a 10% aqueous solution of glutaraldehyde (GA) was alkalized to pH 8.5 in borate buffer solution and heated at 60°C, the ultraviolet spectrum of GA solution showed two distinct absorption maxima. The one at 280 nm with a weak absorbance ascribable to the C=O bond in the aldehyde group shifted to near 300 nm after 50 min with a slight increase in its intensity. Another maximum at 235 nm with a strong absorbance was ascribable to the C=C bond of the α, β-unsaturated aldehyde group which was formed by aldol condensation reaction of GA monomer, and its absorbance increased markedly with increasing reaction time. The high performance liquid chromatography (HPLC) analysis with detection at 235 nm indicated that several GA oligomers were formed by the alkali treatment ad their concentrations increased. The cross-linking ability of these oligomers was examined by immobilizing enzymes (alcohol dehydrogenase (ADH), glutamate dehydrogenase (GLDH)) to an aminated polymer gel matrix by reaction with the treated GA solution. The enzyme activities increased with increasing concentration of GA oligomers. Then, the GA oligomers were isolated and used as the cross-linking agent. The activities of ADH and GLDH were 4-fold and 13-fold higher, respectively, than those obtained by using untreated GA solution, while the total amounts of immobilized enzymes were almost unchanged. These results suggest that GA oligomers may act as cross-linkers in a manner different from the generally accepted Schiff base formation reaction; a possible mechanism may involve addition reaction of an amino group to the double bond in the aldol condensate of GA. This reaction, if it does occur, seems to be effective for the enhancement of the immobilized enzyme activity.View full abstractDownload PDF (614K) -
Takashi ABIKO, Hiroshi SEKINO1989 Volume 37 Issue 9 Pages 2467-2471
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAn analog of thymosin βXen4 isolated from ooxytes of Xenopus laevis, deacetyl-thymosin βXen4, was synthesized by assembling 6 peptide fragments, followed by deprotection with 1 M trifluoromethanesulfonic acid-thioanisole (molar ratio, 1 : 1) in trifluoroacetic acid in the presence of dimethylselenium. Finally, the deprotected peptide was incubated with dithiothreitol to reduce sulfoxide on the methionine side chain. The synthetic tritetracontapeptide was found to have a restoring effect on the impaired blastogenic response of T-lymphocytes isolated from uremic patients.View full abstractDownload PDF (861K) -
Takashi ABIKO, Hiroshi SEKINO1989 Volume 37 Issue 9 Pages 2472-2476
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA heptadecapeptide, H-Arg-Lys-Ala-Val-Tyr-Val-Glu-Leu-Tyr-Leu-Gln-Ser-Leu-Thr-Ala-Glu-His-OH, corresponding to amino acids 32 to 48 of human splenin (hSP) and an analog in which the amino acid residue at position 34 is changed from Ala to Glu, were synthesized. These peptides were synthesized using conventional solution synthesis and were tested for their effect on reduced B-lymphocytes of uremic patients. Incubation of peripheral lymphocytes isolated from uremic patients with these two synthetic heptadecapeptides, hSP fragment 32-48 and [Glu34]hSP fragment 32-48, had an enhancing effect on the reduced B-lymphocytes, but synthetic bovine thymopoietin II (bTP-II) fragment 32-49 had no effect under the same conditions.View full abstractDownload PDF (824K) -
Yoshiaki MATSUMOTO, Yoshiteru WATANABE, Naohide HORI, Seizo NARITOMI, ...1989 Volume 37 Issue 9 Pages 2477-2480
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA hollow-type suppository containing gentamicin (GM) in its cavity was prepared using Witepsol H-15 (H-15) mixed with glyceryl-1-monooctanoate (MO) or MO alone in the body of the suppository (type I) and a suppository (type II) containing GM and MO in the cavity was constructed using H-15 in the body of the suppository.Without MO, GM (60 mg) was not absorbed (plasma GM levels less than 1μg/ml). However, the absorption of GM from the rectum of rabbits was enhanced by coadministered MO in types I and II. Even when the amount of GM was decreased to 6mg (1/10), GM was observed in the plasma (Cmax, 3.5±0.3μg/ml) after administration of the suppository made from MO mixed with H-15. The enhancing effect of MO on the rectal absorption of GM could not be further increased by incorporating an amount of MO larger than approximately 300mg into the suppository.This study demonstrates that MO can be used in the two types of hollow suppositories as an effective enhancing agent of rectal absorption of poorly absorbed drugs such as GM.View full abstractDownload PDF (607K) -
Tsutomu KONNO, Koji KINUNO1989 Volume 37 Issue 9 Pages 2481-2484
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFlufenamic acid (FFA) was mixed with magnesium aluminum silicate (MAS) and stored at 60°C at a reduced pressure of about 2.5 mmHg. After storage, when its concentration was not more than 20%, FFA was observed by X-ray diffraction and polarizing microscopy to be amorphous. The dissolution of FFA was thus enhanced in comparison with that of a freshly prepared mixture. Furthermore, the dissolution curves showed a typical supersaturation pattern, and the supersaturation state continued longer, the higher the pH value of the dissolution medium. Flufenamic acid, in a mixture with MAS, became amorphous more rapidly at reduced pressure than at atmospheric pressure, and therefore the effect improved dissolution appeared earlier at reduced pressure. Infrared spectral studies suggested that FFA, after storage at a reduced pressure with MAS, was dispersed monomolecularly in an ionic form. The technique of treating crystalline medicinals, that have poor solubility in water, with adsorbent at reduced pressure may be useful for improving their dissolution characteristics.View full abstractDownload PDF (743K) -
Susumu KAWASHIMA, Yutaka YAMADA, Kumiko HONDA, Toshiro TABATA, Masaru ...1989 Volume 37 Issue 9 Pages 2485-2490
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSStabilization of bacampicillin (BAPC) in suspension was examined by the addition of alginic acid (Alg). BAPC formed a slightly water-soluble adduct (BAPC-Alg) with Alg, in wich BAPC and Alg were presumed to be linked by ionic bonding. However, the suspension of htis chemically stable adduct showed a similar lability to a suspension of BAPC alone; chemically very unstable particles of BAPC base were deposited in the suspension. In contrast, when BAPC-Alg adduct was suspended in 1.0% Alg colution at the same pH region, the precipitation of the particles of BAPC base were not observed. This stabilization is supposed to be due not only to the chemical stability of the adduct, but also to an inhibition of the deposition of an unstable BAPC base particles by Alg.View full abstractDownload PDF (823K) -
Kazuhiro MORIMOTO, Shinichi FUKANOKI, Katsuaki MORISAKA, Suong-Hyu HYO ...1989 Volume 37 Issue 9 Pages 2491-2495
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSPreparations of beta-blockers, propranolol-HCI and atenolol, in poly(vinyl alcohol) (PVA) hydrogel were designed for the therapeutic treatment of hypertension by transrectal delivery. In vitro release characteristics and plasma drug concentration profiles after rectal administration in rats and dogs were examined. The PVA hydrogels containing β-blockers were prepared by a low-temperature crystallization method. The release of β-blockers from hydrogel preparations was consistent with Fickian diffusion (Higuchi model); the drug release versus the square root of release time profile gave a straight line over 60% of the total release process. The release of β-blockers from hydrogel preparations increased at higher concentrations of PVA in the hydrogel preparations and was not affected by the pH of hydrogel preparations. Plasma concentrations of β-blockers after rectal administration of hydrogels were higher than those after administration of suppositories (Witepsol H-15) in rats and dogs. The drug plasma concentrations increased at higher concentrations of PVA in hydrogel preparations. In the case of propranolol, which is a hepatic high-clearance drug, area under the blood concentration curve, 0-8h after rectal administration of a hydrogel preparation (20% w/w PVA, pH 7.0) was 2.16 times and 5.26 times higher than those obtained with Witepsol H-15 suppository and oral administration, respectively. Rectal administration with PVA hydrogels is a favorable route for a hepatic high-clearance drug such as propranolol.View full abstractDownload PDF (754K) -
Mariko NAGATA, Toshihisa YOTSUYANAGI, Ken IKEDA1989 Volume 37 Issue 9 Pages 2496-2499
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSDiffusion of vitamin K1 solubilized by phosphatidylcholine-sodium deoxycholate mixed micelles through porous membranes having various pore characterisitcs was examined. The membranes include Nuclepore, Duragard and nitrocellulose membranes, which were intended to mimic the narrow channels in the vicinity of absorptive brush border. The diffusino coefficient of the mixed micelles was 4.6-5.5×10-7 cm2/s, from which the hydrodynamic radius was calculated to be about 50Å. The dependence of the diffusivity on pore size showed that the transport of the micelles is hindered by pores having a radus ratio of the diffusate to the pore of about 0.05 or larger.View full abstractDownload PDF (643K) -
Shingo YANO, Masatoshi HARADA, Kazuo WATANABE, Koichi NAKAMARU, Yoshif ...1989 Volume 37 Issue 9 Pages 2500-2504
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSGlycyrrhetinic acid (Ia) and eighteen related derivatives were examined for antiulcer activity using stress-induced gastric lesions (restraint plus water immersion at 25°C) in mice and rats as screening tests. Among the compounds tested, dihemiphthalate derivatives of 18α- or 18β-olean-12-ene-3β, 30-diol (IV, IIId), 18β-olean-9(11)12-diene-3β, 30-diol (VIc), and olean-11, 13(18)-diene-3β, 30-diol (VIIc) showed potent inhibition of gastric lesion formation at a dose of 12 or 25mg/kg (p.o.); carbenoxolone sodium (Ib) significantly suppressed the lesion formation at a dose of 500mg/kg (p.o.). Further evaluation of the antiulcer activity was carried out mainly for compound IIId. Compound IIId (p.o.) prevented the formation of indomethacin-induced or 0.6N HCl-induced gastric lesions; the latter antiulcer effect was noted even in the combined treatment with indomethacin, suggesting that the effect occurs independently of endogenous prostaglandins. In contrast, compound IIId had no preventive effect against Shay rat ulcer when intragastrically (i.g.) administered; further, no antisecretory effect was seen by i.g. application in pylorus-ligated rats. Administration of compound IIId for 2 weeks accelerated the healing rate of acetic acid-induced gastric ulcer in rats. No significant change in urine excretion was observed after its consecutive administration for 3d. These results suggest that dihemiphthalate derivatives (IIId, IV, VIc, VIIc) may produce a strong antiulcer activity, probably by strengthening some gastric mucosal defensive mechanism.View full abstractDownload PDF (798K) -
Zhi-da MIN, Shi-qiang WANG, Qi-tai ZHENG, Binrg WU, Mizuo MIZUNO, Tosh ...1989 Volume 37 Issue 9 Pages 2505-2508
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFrom the ethanol extract of whole herbs of Ajuga decumbens (Labiatae), four new neo-clerodane diterpenoids, named ajugacumbins A, B, C and D (1-4), were isolated. The configuration of 1 was determined to be 6α-acetoxy-4, 17-epoxy-18-tigloyloxy-neo-cleroda-13-en-15, 16-olide by X-ray analysis. THe other structures were also determined by spectroscopic analysis to be 4, 17-epoxy-6α-hydroxy-18-tigloyloxy-neo-cleroda-13-en-15, 16-olide (2), 1α, 3β, 6α-triacetoxy-4, 17-epoxy-18-tigloyloxy-neo-cleroda-13-en-15, 16-olide (3) and 6α-acetoxy-4, 17-epoxy-3β-hydroxy-18-tigloyloxy-neo-cleroda-13-en-15, 16-olide (4). These compounds displayed insect antifeedant activity.View full abstractDownload PDF (648K) -
Shiro ISHIDA, Yoko SAKIYA, Tsutomu ICHIKAWA, Shoji AWAZU1989 Volume 37 Issue 9 Pages 2509-2513
Published: September 25, 1989
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe pharmacokinetics of glycyrrhetic acid (GLA) was examined in rats after bolus i.v. injection at a dose of 2, 5, or 12mg/kg. The decline in plasma concentration was generally biexponential at each dose, but the terminal disposition became much slower with increase of dose. A greater than proportional increase in plasma GLA concentration was observed with increase of dose, suggesting a dose-dependency of GLA disposition. Apparent total body clearance decreased significantly with increase of dose. On the other hand, the apparent steady-state distcibution volume after i.v. administration was unaffected by dose. The plasma disposition at each dose fitted well to a two-compartment pharmacokinetic model with Michaelis-Menten elimination. It was concluded that the pharmacokinetics of GLA in the rat is dose-dependent owing to a saturable elimination rate. THe plasma level of GLA after glycyrrhzin (GLZ) i.v. dosing (100mg/kg) in the control rats (without biliary fistulization) sustained the concentration range of 1.5-3μg/ml during 1-48h, but that in the rats with biliary fistulization declined with time. It was suggested that the sustained plasma level of GLA is accounted for by the intestinal reabsorption of GLA produced from GLZ and GLA-conjugates during the enterohepatic recycling of both.View full abstractDownload PDF (723K)