Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 36, Issue 11
Displaying 1-50 of 59 articles from this issue
  • KATSUMI MATSUZAKI, TETSUROU HANDA, KOICHIRO MIYAJIMA, YASUSHI MIKURA, ...
    1988 Volume 36 Issue 11 Pages 4253-4260
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Hemolysis of rabbit erythrocytes by several lysophosphatidylcholines (lysoPCs) containing C12-C18 saturated and cis unsaturated acyl chains was investigated in vitro. The degree of hemolysis was dependent on the erythrocyte concentration used.Based on this dependency, two determinants for the drugs'hemolytic activity, namely, their affinity for the cell membrane and their intrinsic hemolytic activity, were analyzed separately to clarify the relationship between these factors and the acyl chain structure. Elongation of the acyl chain in saturated lysoPCs was found to greatly increase the affinity and slightly increase the intrinsic activity. In contrast, the introduction of a cis double bond into the acyl chain was found to slightly decrease the affinity and to significantly decrease the intrinsic activity. The affinity and the intrinsic hemolytic activity are discussed in relation to critical micellar concentration and bilayer solubilization ability, respectively.
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  • SHINJI ITOH, HARUMI ICHIKAWA, HIDETOSHI TAKAGI, ITSUO YOSHIZAWA
    1988 Volume 36 Issue 11 Pages 4261-4268
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    17α-Ethyl-17β-methyl-5β-pregn-13-en-3α-ol, a major hydrolysis product of pregnanediol disulfate in 3N hydrochloric acid at 95°C, was shown to be formed via two reaction pathways, a concerted mechanism and a stepwise mechanism involving the C20-carbocation, in an approximate ratio of 75:25.
    D-Homoannulation of the isomeric sulfate, 5β-pregnane-3α, 2β-diol disulfate, giving 17α-methyl-D-homo-5β-androstane-3α-17aβ-diol as a predominant product under the same hydrolysis conditions, was shown to occur mainly (ca.90%) by the concerted mechanism.
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  • AKIRA INADA, MASAAKI YAMADA, HIROKO MURATA, MARI KOBAYASHI, HARUMASA T ...
    1988 Volume 36 Issue 11 Pages 4269-4274
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Two new sulfated glycosides were isolated as major constituents from seeds of Patrinia scabiosaefolia FISCHER (Valerianaceae). These compounds, termed sulfapatrinosides I (1) and II (2), have been established to be 23-sulfates (in the forms of the sodium salts) of 3β-hydroxyurs-12-en-28-oic acid 28-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester and 3β-hydroxyolean-12-en-28-oic acid 28-O-[β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl] ester, respectively, based on chemical and spectral evidence.
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  • YOSHIHISA TAKAISHI, KUNIE UJITA, KIMIKO NAKANO, TOSHIAKI TOMIMATSU
    1988 Volume 36 Issue 11 Pages 4275-4283
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    New sesquiterpene esters designated triptofordins F-1 (1), F-2 (7), F-3 (10), and F-4 (5) were isolated from the leaves of Tripterygium wilfordii HOOK fil. var. regelii MAKINO.Their structures were established by spectroscopic investigation and chemical reactions.The absolute structures of these compounds were determined by using the dibenzoate chirality method.
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  • TAKAO KUROSAWA, MASAHIKO TOHMA
    1988 Volume 36 Issue 11 Pages 4284-4292
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    The bicyclic enones (3 and 14) and the triketone (17), key intermediates for the synthesis of 11-and 12-methylestrones, were prepared by means of the thermal elimination of the β-ketosulfoxides (1 and 12). By a modification of Smith's estrone synthesis, 3 and 14 were transformed to the corresponding 11-and 12-methylestratetraenes (6 and 26), which yielded 11β-, 11β-and 12βmethylestrones (10, 11 and 32b) on selective reduction and demethylation, respectively. The triketone (17) was also converted into 12β-methylestrone (32b) via the selective reduction of 12 Amethylestrapentaene (18). 12α-and 12β-Methylestrones (32a and b) were synthesized from 12α-and 12βA-carboxyestradiol 3-methyl ethers (28a, b) reported previously.
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  • YOSHIMITSU NAGAO, KEIKO INOUE, MASAE YAMAKI, MOTOO SHIRO, SHUZO TAKAGI ...
    1988 Volume 36 Issue 11 Pages 4293-4300
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    rac-4-Methoxycarbonyl-Δ2-1, 3-thiazolines 2a-z and rac-4-methoxycarbony1-1, 3-thiazoline-2-thiones 3a, d-t were examined by carbon-13 and proton nuclear magnetic resonance and ultraviolet spectroscopic methods to provide a basis for spectroscopic identification of Δ2-1, 3-oxazolines and 1, 3-oxazolidine-2-thiones. X-Ray structural analysis of 3-(4'-bromobenzy1)-2-thioxo-1, 3-thiazolidine-4-carboxylic acid 4n was also carried out.
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  • KAZUYUKI HORI, TOSHIKO SATAKE, YASUHISA SAIKI, TAKAO MURAKAMI, CHIU-MI ...
    1988 Volume 36 Issue 11 Pages 4301-4306
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    From the fronds of Dennstaedtia distenta, new flavan-3-ol (catechin) derivatives, distenin (1), its dimer (2) and its trimer (3), were isolated in addition to vitexin. On the basis of the spectroscopicand chemical evidence, their structures were established as (2R, 3R)-flavan-3, 5, 7-triol (1), distenin-(4β→8)-distenin (2) and distenin-(4β→8)-distenin-(4β→8)-distenin (3), respectively.
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  • YOSHIRO MATSUDA, HIROMI GOTOU, YUKIO ONIYAMA, KEISUKE KATOU, HIROSHI M ...
    1988 Volume 36 Issue 11 Pages 4307-4315
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    By the reaction of 6-methyl-4-imino-4H-quinolizine derivatives (5, 8) with the mixed anhydrides (6a-h), 2-phenyl-1-azacycl [3.3.3] azines (7a-p, 9a-g) were obtained.2-Pheny1-1, 3, 6-triazacycl [3.3.3] azine derivatives (15ah, 17a-h, 18a-g) were prepared by the reaction of 2-(2-cyanovinyl) amino-6-aminopyridines (13, 16) with mixed anhydrides (6a-h).The proton nuclear magnetic resonance spectral data of the 2-phenylazacycl [3.3.3] azines (12, 18a) may be interprited in terms of a paramagnetic ring current.
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  • PING LEE, YUKIE KITAMURA, KOH KANEKO, MOTOO SHIRO, GUO-JUN XU, YUH-PAN ...
    1988 Volume 36 Issue 11 Pages 4316-4329
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A novel (22S, 25R)-13, 17-didehydro: 5α-cevanine alkaloid, ebeienine (1), was isolated from the bulbs of Fritillaria ebeiensis var.purpurea, together with (25S)-20-deoxy-5α-cevanin-3, β, 6β-diol (ebeiedine (2)), and (25S)-20-deoxy-5α-cevanin-3α-o1-6-one (ebeiedinone (3)). Their structures were elucidated by physical methods and finally confirmed by X-ray crystal structure determination.
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  • FUMIKO ABE, TATSUO YAMAUCHI
    1988 Volume 36 Issue 11 Pages 4330-4336
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Seven pregnane glycosides including six bisdesmosidic glycosides of teikagenin were isolated and their structures were determined. L-Sarmentose, a new 2, 6-dideoxy-3-O-methylhexose, was found as one of the component sugars.
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  • HIROSHI SUEMUNE, TETSUJI HARABE, ZHUO-FENG XIE, KIYOSHI SAKAI
    1988 Volume 36 Issue 11 Pages 4337-4344
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Asymmetric hydrolysis of 2, 2-bis (acetoxymethyl) cyclopentanone (5) using biocatalysts and its application to a formal synthesis of (-)-malyngolide are described.For the asymmetric induction at the quaternary carbon of 5, cholinesterase from electric eel was found to be effective to afford the (+)-monoacetate (6)(90%ee).Compound (+)-6 was easily converted to the synthetic intermediate (28) for (-)-malyngolide.
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  • KIYOSHI SAKINA, KEIKO KAWAZURA, KAZUYUKI MORIHARA, HARUAKI YAJIMA
    1988 Volume 36 Issue 11 Pages 4345-4354
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Enzymatic condensation by thermolysin between various amino acid amides and Naprotected or unprotected peptides was examined.As models, three protected tetrapeptide amides, Boc-Trp-Met-Asp-X, Boc-Ser-Glu-Ala-X and Boc-Ser-Lys-Ala-X, and two unprotected tetrapeptide amides, H-Trp-Met-Asp-X and H-Phe-Met-Arg-X, were prepared [X=Phe-NH2, Leu-NH2, Phe-NHEt, Val-NH2, Ala-NH2, (p-fluoro) Phe-NH2], and the effects of various experimental conditions (pH, solvent and time) were examined.In addition, the C-terminal of oxidized insulin B-chain was elongated to an amide by addition of various amides mentioned above with the aid of thermolysin.
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  • AKINORI KUBO, YOSHIYASU KITAHARA, SHINSUKE NAKAHARA, RYOICHI IWATA, RY ...
    1988 Volume 36 Issue 11 Pages 4355-4363
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Mimocin, an isoquinolinequinone antibiotic from Streptomyces lavendulae No.314, and its congeners were synthesized.
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  • LILI Guo, EIGORO MURAYAMA, SUSUMU FUNAKOSHI, NOBUTAKA FUJII, MITSURU A ...
    1988 Volume 36 Issue 11 Pages 4364-4376
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A 36-residue peptide amide corresponding to the entire amino acid sequence of chicken antral peptide was synthesized by assembling seven peptide fragments via the azide, followed by thioanisole-mediated deprotection with trimethylsilyl bromide and trimethylsilyl trifluoromethanesulfonate in trifluoroacetic acid.The synthetic peptide stimulated gastric secretion, but not pancreatic secretion.
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  • KAZUO BANNO, TAKAFUMI FUJIOKA, TETSURO KIKUCHI, YASUO OSHIRO, TAKASHI ...
    1988 Volume 36 Issue 11 Pages 4377-4388
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    With the aim of developing a novel neuroleptic drug, a series of ω-(4-phenyl-1-piperazinyl)-alkoxy-2 (1H)-quinolinone derivatives have been synthesized and tested for anti-methamphetamine and anti-epinephrine activities. Most of the derivatives were found to possess a potent antimethamphetamine activity in the jumping behavior test on mice treated with 3-(3, 4-dihydroxyphenyl)-L-alanine (L-DOPA) and methamphetamine, or in the lethality test with methamphetamine-treated mice. They also showed relatively high anti-epinephrine potency depending on the nature or number of substituents on the phenyl group in the 4-phenyl-1-piperazinyl moiety; some of these compounds induced only weak catalepsy in mice. Among them, 7-{3-[4-(2, 3-dimethylphenyl)-1-piperazinyl]propoxy}-2 (1H)-quinolinone (OPC-4392), which was suggested to be a dopamine autoreceptor agonist, was selected for further investigations. The structure-activity relationships are also discussed.
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  • IKUO ADACHI, TERUO YAMAMORI, YOSHIHARU HIRAMATSU, KATSUNORI SAKAI, SHI ...
    1988 Volume 36 Issue 11 Pages 4389-4402
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A series of 4-aryl-4, 7-dihydrothieno [2, 3-b] pyridine-5-carboxylate derivatives (I) was synthesized and tested for binding affinity to Ca2+ channels in rat cerebral cortex membranes, coronary vasodilator effect in isolated guinea pig hearts, and antihypertensive activity in spontaneously hypertensive rats.Several compounds had potent coronary vasodilator and antihypertensive activities.The structure-ctivity relationships of the series indicated that a lipophilic 3-alkyl substituent with moderate bulkiness was effective for enhancing the pharmacological potencies.Among them, methyl 4, 7-dihydro-3-isobuty1-6-methy1-4-(3-nitrophenyl) thieno [2, 3-b] pyridine-5-carboxylate (S-312) was selected as a promising cardiovascular agent.The relationship between the absolute configuration of S-312 and its biological activities is also presented.
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  • SHENG-CHU KUO, SHANG-YUAN TSAI, HAN-TEH LI, CHUN-HSIUNG WU, KATSUMI IS ...
    1988 Volume 36 Issue 11 Pages 4403-4407
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A series of furo [2, 3-b][1, 8] naphthyridine-3, 4 (2H, 9H)-dione and 4H-furo [2, 3-d] pyrido [1, 2-a] pyrimidine-3, 4 (2H)-dione derivatives were synthesized and evaluated for antiallergic activity by rat passive cutaneous anaphylaxis (PCA) screening.Most of these compounds were found to be orally active.Among them, 9-ethyl-7-methylfuro [2, 3-b][1, 8] naphthyridine-3, 4 (2H, 9H)-dione was the most promising, and was selected for further modifications.
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  • HITOSHI ISHIDA, TOMOHIKO YAMAGUCHI, RYUKAN NATSUYAMA, KUNIRO TSUJI, TA ...
    1988 Volume 36 Issue 11 Pages 4408-4413
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Sodium scymnol sulfate, which is a major component in bile of Rhizoprionodon acutus, was isolated by 3 steps of chromatography to afford 753 mg of the bile salt from 5 gallbladders (65 g), and its structure was determined to be 3α, 7α, 12α, 24, 26-pentahydroxy-5β-cholestan-27-yl sodium sulfate, on the basis of chemical and physical data.
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  • HITOSHI ISHIDA, TAKAYUKI UMINO, KUNIRO TSUJI, TAKUO KOSUGE
    1988 Volume 36 Issue 11 Pages 4414-4420
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    By following the antihemorrhagic activity according to Tajima's method, two antihemorrhagic principles, a new flavonol glucoside (1) and an unknown compound (2), were isolated from the dried pollen of Typha lactifolia L., which is one of the most important herbs for treatment of stagnant blood and bloody stools in traditional Chinese medicine.The structure of 1 was established as isorhamnetin 3-rutinoside-7-rhamnoside (3-[6-O-(6-deoxy-α-L-mannopyranosyl)-β-D-glucopyranosyl] Oxy-5-hydroxy-7-[β-L-mannopyranosyl] oxy -2-(4-hydroxy-3 -methoxyphenyl)-4H-1-benzopyran-4-one), based on chemical transformations and spectral data.
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  • SHOICHI KANATOMO, AKIMORI WADA, YUKA HAMAOKA, SOTOO NAGAI, SHIZUO FUKU ...
    1988 Volume 36 Issue 11 Pages 4421-4425
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Various (E)-β-(pyrimidin-5-yl) acrylamides (4 and 5) were synthesized as sparsomycin analogs, and the relationship between chemical structure and antitumor activity was examined.Synthesis involved condensation of appropriate acids (3) and methyl methioninate (L and D isomers) by the mixed anhydride method using isobutyl chlorocarbonate.The antitumor activity was studied by [methyl-3H] thymidine incorporation assay with mouse leukemia L5178Y cells in vitro.The concentrations in μg/ml required for 50% inhibition of incorporation by compounds 4b, 4f, g, 5b, and 5f, g, which have no substituent at the 2 or 6 position on pyrimidine ring, were particularly high. Thus, such substituents enhanced antitumor activity, although the activity was almost uninfluenced by changes of the alkoxy group as a substituent.
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  • YUSUKE AMINO, KAZUHIRO KAWADA, KOJI TOI, IZUMI KUMASHIRO, KOJI FUKUSHI ...
    1988 Volume 36 Issue 11 Pages 4426-4434
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    The adjuvant effect of N-acyl-L-and D-phenylalanine derivatives on intestinal absorption of insulin was investigated in normal mice. The correlation between the chemical structural properties of the N-acyl moiety and the absorption-promoting activity was estimated from the glucose concentrations and the insulin levels in the blood of mice after oral combined administration of insulin and adjuvant. The chemical structural properties of N-acyl-phenylalanine derivatives necessary for adjuvant effect on intestinal absorption of insulin were as follows.
    1. An aromatic ring is present, separated by two atoms from the acyl carbonyl group.
    2. Either of X or Y is oxygen or X-Y is a double bond in Fig.2.
    3. The N-acyl moiety has small hydrophobic substituents, such as F, Cl, or Me at Rα, Rβ, Rη and has an appropriate hydrophilic-hydrophobic balance of the overall molecule.
    The use of these agents to enhance insulin absorption offers the possibility of a new approach to oral insulin therapy.
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  • MASAHIKO SEKI, TAMON MORIYA, KAZUO MATSUMOTO, KOHKI TAKASHIMA, TETSUJI ...
    1988 Volume 36 Issue 11 Pages 4435-4440
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A series of 2-aryl and 2-alkyl derivatives of 5-alkyl-4-oxazoleacetic acids was synthesized and tested for hypolipidemic activity. Among them, 5-isopropyl-2-(4-fluorophenyl)-4-oxazoleacetates exhibited potent activities, being more active than clofibrate [ethyl 2-(4-chlorophenoxy) isobutvrate].
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  • HIDEJI ITOKAWA, JUNPING XU, KOICHI TAKEYA
    1988 Volume 36 Issue 11 Pages 4441-4446
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Four new pregnane glycosides, named periplocosides J, K, F and O, have been isolated from the antitumor fraction of Periploca sepium (Asclepiadaceae). Their structures were established by various nuclear magnetic resonance techniques and chemical evidence.
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  • MINEO SHIMIZU, HISASHI SHOGAWA, TOSHIMITSU HAYASHI, MUNEHISA ARISAWA, ...
    1988 Volume 36 Issue 11 Pages 4447-4452
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    The 70% EtOH extract of the aerial parts of Catasetum barbatum LINDLE showed inhibitory effects on carrageenin-induced paw edema when topically applied to rats and on histamine-induced contraction in guinea pig ileum.
    Four compounds including a new phenanthrene, 2, 7-dihydroxy-3, 4, 8-trimethoxyphenanthrene (2), were isolated from the active fraction. 2, 7-Dihydroxy-3, 4-dimethoxyphenanthrene (1) showed inhibitory effects in both biological assays.
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  • TOHRU SUGIMOTO, TOSHIO MIYASE, MASANORI KUROYANAGI, AKIRA UENO
    1988 Volume 36 Issue 11 Pages 4453-4461
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Four new limonoids and five new quinolone alkaloids were isolated from the fruit of Evodia rutaecarpa BENTHAM (Rutaceae), together with seven known limonoids and four known quinolone alkaloids, and their structures were determined on the basis of spectral data and chemical reactions.
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  • MASAO HATTORI, TOMOYUKI KANDA, YUE-ZHONG SHU, TERUAKI AKAO, KYOICHI KO ...
    1988 Volume 36 Issue 11 Pages 4462-4466
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    The C-glucosyl bond of barbaloin, a major purgative principle of aloe, was cleaved with human intestinal bacteria under anaerobic conditions, yielding aloe-emodin anthrone and aloeemodin bianthrone. Fecal flora of humans had the most potent transforming activity but those of rats and mice had less or no activity.
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  • MASAO HATTORI, YUKIO KAWATA, NOBUKO KAKIUCHI, KENJI MATSUURA, TSUYOSHI ...
    1988 Volume 36 Issue 11 Pages 4467-4473
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Qualitative analysis of crude saponin fractions from Panax ginseng, Panax japonicus and Bupleurum falcatum, as well as authentic saponins, was performed with a new type of liquid chromatography/mass spectrometry (LC/MS) system equipped with a frit-fast atom bombardment (FRIT-FAB) interface. The separation of saponins was achieved on a semi-micro column by gradient high performance liquid chromatography using an acetonitrile and water system as a mobile phase, and the elution profile was monitored by fast atom bombardment mass spectrometry (FAB-MS). The peaks were readily identified from their retention times and negative ion FAB spectra. Thus, LC/MS in the gradient-elution mode was demonstrated to be useful for qualitative analysis of saponins in crude drugs.
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  • SU-LAN HSIU, HIDEKO KAWAKI, KEIKO YOKOYAMA, HITOSHI TAKAI, YOSHIO SASA ...
    1988 Volume 36 Issue 11 Pages 4474-4477
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    Under apolar conditions, the logarithm of the relative retention values log γ of substituted η-propane and n-butane derivatives can be expressed by a linear combination of the substituent entropy constant δs°and descriptor μ2/α. There seems to be a clear physical basis for this result in terms of the enthalpy of dissolution, ΔH°s.
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  • TERUYOSHI MARUNAKA, EIJI MATSUSHIMA, YOSHINORI MINAMI, KEN-ICHIRO YOSH ...
    1988 Volume 36 Issue 11 Pages 4478-4487
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    (2S, 3R, 5S)-3-Methyl-7-oxo-3-(1H-1, 2, 3-triazol-1-yl-methyl)-4-thia-l-azabicyclo [3.2.0]-heptane-2-carboxylic acid 4, 4-dioxide (YTR-830H) is a new β-lactamase inhibitor. The degradation of this β-lactamase inhibitor in several buffer solutions, NaOH aqueous solution and NaOH-saturated methanol solution was investigated. In the initial step of degradation in aqueous solutions, YTR-830H was degraded to 2-amino-3-methyl-3-sulfino-4-(1H-1, 2, 3-triazol-1-yl)-butyric acid (YTR-830H-II) and formylacetic acid (YTR-830H-III) through (E)-5-methyl-5-sulfino-6-(1H-1, 2, 3-triazol-l-yl)-3-aza-l-heptene-1, 4-dicarboxylic acid (YTR-830H-I) as an intermediate. The YTR-830H-II in all solutions then proceeded to an unidentified product, YTR-830HIIa. In acidic solution it was converted to 1, 2, 3-triazole and several unidentified products (YTR-830H-IIa, -IIb, -IIc and-IId). Degradation at various pHs showed different patterns and rates. Following degradation in NaOH-saturated methanol solution, 1-methyl hydrogen (E)- and (Z)-5-methyl-5-sulfino-6-(1H-1, 2, 3-triazol-1-yl)-3-aza-1 -heptene-1, 4-dicarboxylic acid (YTR-830H-Ia and Ib) were detected.
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  • KIYOSHI ZAITSU, KAYOKO YAMAGISHI, YOSUKE OHKURA
    1988 Volume 36 Issue 11 Pages 4488-4493
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A sensitive assay method for adenosine deaminase activity in human serum is described based on the flow-injection determination of inosine formed enzymatically from substrate adenosine. Serum (10μl) is incubated with adenosine in the presence of urate oxidase and catalase, and the resulting mixture, after deproteinization with perchloric acid, is introduced into a flow-injection system in which immobilized enzyme columns of purine nucleoside phosphorylase, xanthine oxidase, urate oxidase and horseradish peroxidase are connected in series in that order in the flow line. Hydrogen peroxide formed in the enzymatic conversion of inosine is measured fluorimetrically by reaction with 3-(p-hydroxyphenyl) propionic acid in the system. The lower determinable limit of adenosine deaminase activity is 0.17 U/1 serum.
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  • EISUKE SATO, YUICHI KANAOKA
    1988 Volume 36 Issue 11 Pages 4494-4498
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    As a part of the development of a sensitive fluorometric assay for the activity of carboxypeptidase A, bimane-peptides containing tryptophan, i.e., S-[9, 10-dioxa-syn-(methyl, methyl).-(methylene, methyl)-bimane]-thioglycoly1-(glycyl)-L-tryptophan and O-{S-[9, 10-dioxa-syn-(methyl, methyl)(methylene, methyl)-bimane]-thioglycolyl}-DL-3-indolelactic acid, were prepared and shown be good fluorogenic substrates for microdetermination of carboxypeptidase A activity.
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  • YUMI YOKOYAMA, IWAO OHMORI, KOHFUKU KOHDA, YUTAKA KAWAZOE
    1988 Volume 36 Issue 11 Pages 4499-4504
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
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    A 25-kilodaltons (kDa) protein was isolated from the parasporal inclusion produced from Bacillus thuringiensis subsp.israelensis.This 25-kDa protein inhibited the growth of cultured L1210 murine leukemia cells;IC50of the purified 25-kDa protein was 0.9 μg/ml.This toxic protein interacted with membrane constituent lipids.When the 25-kDa protein was used in combination with anti-cancer drugs, their cytotoxicities against cultured L1210 cells were enhanced.Among the anti-cancer drugs tested, the greatest potentiating effect was found in the case of bleomycin.At a non-toxic dose (0.7μg/ml), the 25-kDa protein potentiated the bleomycin cytotoxicity 6.4 fold. Under the conditions used, the order of potentiation among the anti-cancer drugs tested was as follows: bleomycin (6.4fold), tegafur (4.6), vincristine (4.1), 5-fluorouracil (3.7), vinblastine (3.3), methotrexate (2.5), doxorubicin (2.3), triethylene thiophosphoramide (2.2), neocarzinostatin (2.2) and 1-(4-amino-2 methylpyridine-5-yl) methy1-3-(2-chloroethyl)-3-nitrosourea (1.3).In the case of mitomycin C, the 25-kDa protein was not effective.
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  • TOSHIHIRO OHMORI, KOHJI TAMURA, HIROAKI TAKAOKA, TADANORI SAWAI, GOSEI ...
    1988 Volume 36 Issue 11 Pages 4505-4511
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    A protein-bound polysaccharide (SN-C) obtained from the culture filtrate of Cordyceps ophioglossoides, which has been reported to have antitumor activity, was analyzed for sugar and amino acid components.Gas chromatography revealed that the neutral sugar component of SN-C was mainly composed of glucose.By using an amino acid auto analyzer, it was shown that SN-C was composed of galactosamine as the sole aminosugai.An intraperitoneal administration of SN-C into mice inoculated intraperitoneally with syngeneic murine tumors such as MM46 mammary carcinoma or L5178Y leukemia suppressed the tumor growth and resulted in a significant prolongation of the life span.When used in vitro, SN-C significantly inhibited the proliferation of various murine tumor cells including P388.Futhermore, SN-C inhibited the incorporation of glucose into Meth-A tumor cells with a consequent decrease of deoxyribonucleic acid (DNA) synthesis.SN-C may be a new type of antitumor polysaccharide since this material seems to posess both direct antitumor effect and stimulating activity on the host-mediated effect.
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  • TOSHIHIRO OHMORI, KOHJI TAMURA, AKINORI WAKAIKI, GOSEI KAWANISHI, SUMI ...
    1988 Volume 36 Issue 11 Pages 4512-4518
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    A glucan moiety (CO-1) was dissociated from the antitumor protein-bound polysaccharide (SN-C) obtained from the culture of Cordyceps ophioglossoides by ultrasonication and heat treatment.CO-1 exhibited antitumor activity against murine sarcoma 180 when given by oral administration.CO-1 was also effective against syngeneic MM46 mammary carcinoma (solid form), but did not show any effect on ascitic tumors such as P388 leukemia.On intraperitoneal administration to normal mice, CO-1 increased the number of peritoneal exudate cells and strongly enhanced the chemiluminescence response of these exudate cells.The activity of CO-1 was higher than that of zymosan-A.
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  • MASATOSHI BEPPU, Yuzo FUKATA, KIYOMI KIKUGAWA
    1988 Volume 36 Issue 11 Pages 4519-4526
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Reaction of bovine serum albumin (BSA) with malondialdehyde (MDA), a product of lipid oxidation, resulted in the modification of amino residues of the protein to produce three kinds of adducts in the protein molecules, aminopropenal (1), N, N'-disubstituted 1-amino-3-iminopropene and 4-methyl-1, 4-dihydropyridine-3, 5-dicarbaldehyde (3).Modified BSA, in which 39 out of the total of 60 amino residues were modified, showed effective binding to thioglycollate-induced mouse peritoneal macrophages.MDA-modified BSA inhibited the binding of formaldehyde-modified BSA to the macrophages, indicating that MDA-modified BSA binds to the scavenger receptor for formaldehyde-modified BSA.However, the converse was not the case, suggesting that MDAmodified BSA binds to additional receptors to which formaldehyde-modified BSA does not. Reduction of the double bonds of 1 and 2, and the aldehyde functions of 1 and 3 in MDA-modified BSA did not affect the binding of the protein.However, modification of the aldehyde function of1 with glycine resulted in loss of the ligand activity of the protein.These results suggest that adducts 1, 2and3 in the BSA molecule are not directly involved in the binding to the scavenger receptor of macrophages, though adduct 1 may be located near the binding site or may play a role in maintaining the active conformation of the binding site.
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  • SHUICHI MIYAURA, KIYOKO HORIE, HIDEO ISONO
    1988 Volume 36 Issue 11 Pages 4527-4533
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    We previously reported that the purified glutathione S-transferases from rabbit liver are homodimers or heterodimers of four different subunits, having molecular weight of 24500 (Y1), 25000 (Y2), 26500 (Y3) and 28000 (Y4).Their subunit compositions were also reported to be Y1Y1 (R1a), Y1Y3 (R3a), Y3Y3 (R3b), Y2Y2 (R2) and Y2Y4 (Rib, Ric, Rid).
    In the present study, two additional isozymes, R3o and R3c, were obtained.They showed the same subunit compositions as R la and R3b, respectively.Each subunit with the same molecular weight among different isozymes was demonstrated to have the same pI value by isoelectric focusing on polyacrylamide-gel plates containing 7.5m urea (Y1, pI 8.49;Y2, pI 7.86;Y3, pI 8.41; Y4, pI 7.15).R3a (Y1Y3) in a reconstitution experiment using 4 M guanidine hydrochloride gave Y1Y1 homodimer (R3o), Y1Y3 heterodimer (R3a) and Y3Y3 homodimer (R3b).Similarly, the reconstituted Ric (Y2Y4) gave Y2Y2 homodimer (R2), Y2Y4 heterodimer (Ric) and an isozyme which probably has the subunit composition of Y4Y4.The failure of the in vitro formation of heterodimers such as Y1Y2, Y1Y4, Y2Y3 and Y3Y4 suggests that the possible combinations of subunits are limited.
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  • KOICHI SAKURAI, TOSHIAKI MIURA
    1988 Volume 36 Issue 11 Pages 4534-4538
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Release of iron from ferritin and deoxyribose degradation were caused by alloxan in the presence of reduced glutathione (GSH).Superoxide dismutase, catalase, diethylenetriaminepentaacetic acid and hydroxyl radical scavengers such as mannitol and benzoate inhibited the degradation of deoxyribose in the alloxan-GSH system, suggesting that hydroxyl radical was generated in the alloxan-GSH system in the presence of ferritin.Iron released from ferritin may catalyze hydroxyl radical generation via the Haber Weiss reaction.However, the inhibition of the iron release from ferritin in the alloxan-GSH system required a large amount of superoxide dismutase.These results suggest that the iron release from ferritin in the alloxan-GSH system is not primarily due to superoxide.These findings may help to explain the precise mechanism of alloxan toxicity.
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  • Purification and Characterization
    SUSUMU OGUSHI, HIROAKI WATANABE, MASAO NAKAYAMA, DAISUKE TSURU
    1988 Volume 36 Issue 11 Pages 4539-4546
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    An enzyme which hydrolyzes salicylurate (salicyluric acid) into salicylic acid and glycine was found in a cell-free extract of an intestinal bacterium in rabbit.This enzyme, tentatively named salicylurate-hydrolyzing enzyme, was found to be membrane-bound and was purified from the extract by ammonium sulfate fractionation and column chromatography.Two protein fractions with the enzyme activity were observed on diethylaminoethyl-Toyopearl.The first peak (enzyme I) was further purified by chromatography on carboxymethyl-cellulose and on hydroxyapatite, and its enzymatic properties were characterized.The isoelectric point was 8.7, and the molecular weight was estimated to be 170000 by gel filtration on Sephadex G-150 and 27000 by sodium dodecyl sulfate gel electrophoresis, suggesting that the enzyme exists as a hexamer.The enzyme was strongly inhibited by p-chloromercuribenzoate (PCMB), Hg2+and o-phenanthroline.The activities lost on incubation with PCMB and o-phenanthroline were restored by the addition of 2-mercaptoethanol and Zn2+, respectively.The enzyme catalyzed hydrolysis of N-benzoyl (Bz) amino acids and their derivatives, while it was inert toward n-benzoyl-protected peptides such as p-HO-Bz-Gly-Gly and Bz-Gly-L-His-L-Leu.We conclude that salicylurate hydrolase presented here is a kind of hippurate hydrolase (EC 3.5.1.32).
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  • YAYOI HAYASHI, JUN WATANABE, SHOJI OZEKI, KIKUO IWAMOTO
    1988 Volume 36 Issue 11 Pages 4547-4553
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Salivary excretion profiles of 5-fluorouracil (5-FU) were investigated following bolus intravenous administration at three dose levels (12.5, 25, and 50 mg/kg) in rats. Mandibular (M) and parotid (Pr) saliva samples were periodically collected separately via cannulas inserted into the ducts by stimulating salivation with pilocarpine infused intravenously. Simultaneously, salivary pH, flow rate, and protein concentration were determined.
    (1) Plasma and saliva 5-FU concentration decreased bi-exponentially with time. A relatively scattered relationship but a statistically significant correlation was found between each of the saliva concentrations and plasma 5-FU concentration (p<0.01).(2) The saliva/plasma concentration ratios (S/P ratios) and salivary pH were higher in M than Pr saliva, in contrast to the results in beagle dogs.(3) The S/P ratio and salivary clearance of 5-FU were larger at higher dose, and decreased with the decline of plasma 5-FU concentration, though they showed large fluctuations. It was, therefore, suggested that non-linear kinetics might be involved in the salivary excretion of 5-FU in rats.(4) The contribution of total salivary clearance to total body clearance of 5-FU was found to be insignificant, i.e. less than 0.1 % even at the highest dose.
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  • Methyl Oranie Systems
    YOSHINOBU NAKAO, KEIJI YAMAMOTO, KATSUHIDE TERADA, MANABU SAKAI
    1988 Volume 36 Issue 11 Pages 4554-4559
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Photoacoustic (PA) spectral measurements in the visible region were made for methyl orange contained in physical mixtures with α- and β-cyclodextrins, ground mixtures, and the inclusion compounds.Inclusion of methyl orange in β-cyclodextrin (molar ratio 1: 1) was confirmed by the Bs type phase solubility diagram.The inclusion compounds of α- and β-cyclodextrins showed very similar PA patterns (λmax at 445nm) which were different from the pattern of the physical mixture (λmax at 395nm).The physical mixture showed a gradual change of its PA pattern to that of the inclusion type as a function of grinding time.The pattern of the ground mixture was broader than that of the inclusion compound, but became coincident with it after storage at 40°C and 96% relative humidity for 4d.
    It was concluded that PA spectral measurement is an effective method to investigate inclusion phenomena in the solid state.
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  • HAJIME KOTAKI, TAKAO AOYAMA, FUTAMI NAKAZATO, YUKIYA SAITOH, FUJIO NAK ...
    1988 Volume 36 Issue 11 Pages 4560-4566
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Interactions between methylphenidate (MPD) or its metabolite, ritalinic acid (RA), and pemoline in rats were investigated.At 20min after intravenous administration of 3mg/kg dose of pemoline as a loading dose, constant infusion at a rate of 139μg/h of the drug was carried out to give steady-state plasma level.In intravenous administration of 1mg/kg dose of RA during the constant infusion of pemoline, the plasma concentration of pemoline before and after the administration of RA did not change.Steady-state pemoline also did not affect the pharmacokinetics of RA.Onthe other hand, in intravenous administration of 1mg/kg dose of MPD during the constant infusion of pemoline, the plasma concentration of pemoline slightly increased within 15min after the administration of MPD.Thereafter the concentration of pemoline returned to the level before the superimposition of MPD within 60min. The liver-, kidney-, lung-, muscle- and blood cell-to-plasma concentration ratios of pemoline at 5min after the administration of MPD became smaller compared with those of pemoline in the absence of MPD, and those of pemoline at 60min after the administration were approximately the same as those of pemoline in the absence of MPD. Steady-state pemoline did not affect the pharmacokinetics and tissue distribution of MPD. The increase of plasma concentration of pemoline caused by the superimposition of MPD may result in the displacement of pemoline from tissues and blood cell and/or MPD may inhibit the metabolism of pemoline.
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  • JUNZO SUZUKI, TAKESHI WATANABE, KAORU SATO, SHIZUO SUZUKI
    1988 Volume 36 Issue 11 Pages 4567-4575
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Naphthols were irradiated with ultraviolet light in aqueous nitrite solution under air, oxygen and nitrogen atmospheres. 2-Naphthol gave a mutagenic product in an amount proportional to the irradiation time under air. The mutagen formation was greatly accelerated under oxygen, whereas irradiation under nitrogen gave no mutagen. 1-Naphthol gave scarcely any mutagen under any conditions. The photoreactions of naphthols in the presence and absence of nitrite under the three conditions were analyzed by high performance liquid chromatography in terms of degradation of naphthols and production of nitrosonaphthols, nitronaphthols, quinones and isocoumarin. It was proved that the reactions of nitration and naphthoquinone production both require oxygen. Consequently, the oxygen requirement for mutagen formation was attributable to those for nitration and quinone production from 2-naphthol. Nitronaphthols were presumed to be produced directly by the reaction of photo-induced naphthoxy radical with NO2 radical formed by oxidation of photo-induced NO radical. Both 1, 2-and 1, 4-naphthoquinones were found to be converted photochemically to photo-stable isocoumarin, which exhibited only ambiguous mutagenicity, at different rates. 1-Naphthol, compared with 2-naphthol, was hardly nitrated and was easily converted to isocoumarin, and such reactivity was presumed to be the main reason for the lack of mutagen formation.
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  • YOSHIO TAKEDA, TETSURO SHINGU, TERUYOSHI ICHIHARA, TETSURO FUJITA, TOS ...
    1988 Volume 36 Issue 11 Pages 4576-4580
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The structure of inflexin isolated from Rabdosia inflexa (THUNB.) HARA was re-examined by means of 1H two-dimensional correlated spectroscopy (1H-COSY) and nuclear Overhauser effect (NOE) experiments, and was revised to 1 from the previously reported structure, 2. The structures the chemically correlated diterpenoids, inflexinol and inflexanin B were also revised to 3 and 4, respectively.
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  • CHUZO IWATA, YOSHIJI TAKEMOTO, HITOSHI KUBOTA, MINORU YAMADA, SHUJI UC ...
    1988 Volume 36 Issue 11 Pages 4581-4584
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    (2RS, 5RS, 6SR, 8RS, 10SR)-6-Hydroxymethy1-8-methoxymethoxy-10-methyl-2-pivaloyloxyspiro [4.5] decane (4a), a key intermediate for the synthesis of the spirovetivane sesquiterpenes, i.e.(±)-lubiminol and (±)-oxylubimin, was synthesized.A stereoselective 1, 2-reduction of the enone (6) followed by oxygenation of the C6-methyl group afforded 10. Subsequent hydrogenation of C6-C7 double bond in 10 gave 4a exclusively.
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  • HITOSHI ISHIDA, TAKAYUKI UMINO, KUNIRO TSUJI, TAKUO KOSUGE
    1988 Volume 36 Issue 11 Pages 4585-4587
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The antihemorrhagic principle in Nelumbins Receptaculum, dried receptacle of Nelumbo nucifera GAERTNER, was isolated by a combination of partition, gel filtration through Sephadex LH-20 and column chromatography over silica gel, and identified as quercetin [2-(3, 4-dihydroxy)-3, 5, 7-trihydroxy-4H-1-benzopyran-4-one].
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  • TAICHI OHMOTO, TAMOTSU NIKAIDO, KAZUO KOIKE, KUNIKO KOHDA, USHIO SANKA ...
    1988 Volume 36 Issue 11 Pages 4588-4592
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The structure-inhibitory activity relationships were studied in analogous alkaloids from Picrasma quassioides and Ailanthus altissima, and their derivatives. Altogether, 53β-carboline, 18 canthinone and 7 dimeric alkaloids were tested for cyclic adenosine monophosphate (cAMP) phosphodiesterase inhibition. Major alkaloids (10, 63 and 74) among the three groups of congeners in Picrasma quassioides and Ailanthus altissima showed the most potent inhibitory activity, equal to or greater than that of papaverine used as a reference.
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  • EIJI MATSUSHIMA, KEN-ICHIRO YOSHIDA, RYOTARO AZUMA, YOSHINORI MINAMI, ...
    1988 Volume 36 Issue 11 Pages 4593-4596
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    (2S, 3R, 5S)-3-Methy1-7-oxo-3-(1H-1, 2, 3-triazol-1-yl-methyl)-4-thia-l-azabicyclo [3.2.0] heptane-2-carboxylic acid 4, 4-dioxide (YTR-830H) is a new β-lactamase inhibitor.It was found that the thermal degradation of powdered or lyophilized samples of YTR-830H produced (Z)-3-methyl-4-(1H-1, 2, 3-triazol-1-y1)-2-butenoic acid (YTR-830H-IV), 2-amino-3-methyl-3-sulfino-4-(1H-1, 2, 3-triazol-1-y1)-butyric acid (YTR-830H-II) and its related degradation products, andformylacetic acid (YTR-830H-III).
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  • YASUHIRO KOHAMA, SHIGEKI KUWAHARA, KOHJI YAMAMOTO, MASARU OKABE, TSUTO ...
    1988 Volume 36 Issue 11 Pages 4597-4599
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The present investigation was done to examine whether or not the presence of hydroxyproline in N-3-(4-hydroxyphenyl) propionyl Pro-Hyp-Gly-Ala-Gly (HP-5) is essential for the antiarrhythmic activity. Pretreatment of mice with 10 mg/kg of [Pro2]-HP-5 provided significantly better protection against calcium-induced arrhythmias than did pretreatment with HP-5. Thus, the prolyl residue was more favorable than the hydroxyprolyl residue for antiarrhythmic activity of these analogues.
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  • CHRISTINE PIRAUBE, ERIC POSTAIRE, JEAN MARC LIZE, PATRICE PROGNON, DOM ...
    1988 Volume 36 Issue 11 Pages 4600-4602
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    Chemical instability of liposomes containing dipalmitoylphosphatidylcholine (DPPC), distearoylphosphatidylcholine (DSPC) and soybean phosphatidylcholine (4: 4 2, w/w) was examined.
    Various methods were employed to evaluate the phospholipids degradation: peroxidation index, malondialdehyde determination, reverse-phase high-performance liquid chromatography of DSPC and DPPC, thin layer chromatography of lysophosphatides and gas chromatography-mass spectrometry of free and total fatty acids. Formation of palmitoyllysophosphatidylcholine and stearoyllysophosphatidylcholine was detected within one month during storage.
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  • KIYOTO EDO, KUNIHITO SAITO, MAYUKO KATO, YURIKO AKIYAMA-MURAI, HIDEAKI ...
    1988 Volume 36 Issue 11 Pages 4603-4607
    Published: November 25, 1988
    Released on J-STAGE: February 08, 2011
    JOURNAL FREE ACCESS
    The extra-weak chemiluminescence (CL) of the antitumor antibiotic neocarzinostatin (NCS) in buffer was measured in order to evaluate the stability of NCS injection. Under conditions where NCS is labile, such as heat treatment, high pH or the presence of a thiol compound, NCS generated higher extra-weak CL than under conditions where it is stable (0.1M acetate buffer pH 4.0). On the other hand, the extra-weak CL generated from NCS in buffer decreased in the presence of disaccharides such as sucrose and maltose, which are known to stabilize NCS. This CL measurement may be used as a monitor for evaluating the stability of injections as well as solid drugs such as tablets, capsules, etc., as reported previously (Mizugaki et al., 1985).
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