Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 46, Issue 9
Displaying 1-32 of 32 articles from this issue
  • Mayuko TAKEDA-SHITAKA, Hideaki UMEYAMA
    1998 Volume 46 Issue 9 Pages 1343-1348
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    The catalytic triad consisting of His57, Asp102 and Ser195, which is completely conserved within the chymotrypsin-like serine protease family, plays a central role in catalysis. Highly conserved Ala55 also likely plays an important role in catalysis due to its location just behind the catalytic triad. The only exception to the conserved Ala55 in mammalian serine proteases is Val55 in bovine protein C. Interestingly, it has been demonstrated that the replacement of Ala55 with Thr results in the reduced activity of plasmin in patients with venous thrombosis and with retinochoroidal vascular disorders, which indicates the importance of Ala55 in catalysis. In the present study, we constructed a bovine protein C model which shows that Val55 causes no serious rearrangement of the catalytic site structure. We also constructed an A55T variant model of trypsin for comparison. The A55T substitution alters His57 into an inactive conformation, forming an unusual hydrogen bond between Thr55 Oγ1 and His57 Nε2. The present study shows that the Ala/Val55 residue contributes heavily to the active conformation of His57 and enables His57 to accept a proton from Ser195 Oγ effectively.
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  • Shigenori OKA, Yuji KITAMURA, Masakazu NAGASAWA, Minoru KASHIMOTO, Kun ...
    1998 Volume 46 Issue 9 Pages 1349-1355
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    It has been proposed that a heme-peroxide complex is formed as an intermediate state in the enzymatic reaction. Since the axial position of the heme in tryptophan 2, 3-dioxygenase (TDO) is occupied with a nitrogenous ligand from histidine residue, we studied the heme-peroxide complexes with an axial nitrogenous ligand at the fifth position in a chemical model for TDO. Addition of N-methyl-imidazole to a ferric high-spin porphyrin exhibited ESR spectrum due to a formation of ferric low-spin complex (complex A). Following addition of tetramethylammonium hydroxide to the reaction mixture, the signal due to a different ferric low-spin complex (complex B) appeared. When 3-methylindole (skatole; SK) was added to the resulting solution followed by introduction of dry oxygen gas, a new ESR signal due to a ferric low-spin complex (complex C) was detectable. A similar ESR signal was observed when N-acetyl-tryptophan ethyl ester was used in place of Sk (complex D). Bohan plotting of the crystal-field parameters as a rhombicity-tetragonality diagram obtained from ESR g-values for the complexes (A, B, C, D) revealed that these heme iron complexes can be classified into three groups having N-Fe-N (complex A), N-Fe-O (complex B), and N-Fe-OO (complexes C, D) coordinations. Product analyses for the same reaction systems demonstrated the conversion of each substrate to the dioxygenated product.
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  • Yoshie HORIGUCHI, Akio TOEDA, Katuhiro TOMODA, Hideki SUZUKI, Takehiro ...
    1998 Volume 46 Issue 9 Pages 1356-1363
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Diels-Alder reaction of 4-hydroxy-2-phenylquinolinequinone (10a) and 4-methoxy-2-phenylquinoline-quinone (10b) with 1-methoxy-3-trimethylsilyloxybutadiene proceeded in a highly regio- and stereoselective manner to give the [4+2] adducts (11) and (14) in good yields, respectively. The structures of the adducts and their derivatives were unambiguously determined by spectroscopic data, including high resolution heteronuclear multi bond correlation. The quinolinequinones (10a and 10b) gave inverse regioselectivity. This is related to the presence of the hydroxy group or the methoxy group at the C-4 position. These results demonstrated that Diels-Alder reaction of azadienophiles with activated dienes provides a versatile method for synthesizing 4-oxygenated 1-azaanthraquinones.
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  • Tadashi SHIRAIWA, Masanori OHKUBO, Motoki KUBO, Hideya MIYAZAKI, Masak ...
    1998 Volume 46 Issue 9 Pages 1364-1369
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    To synthesize four stereoisomers of 2-amino-3-[(1, 2-dicarboxyethyl)sulfanyl]propanoic acid (ADC), (RS)-mercaptosuccinic acid [(RS)-MSA] was optically resolved using (1S, 2S)-2-amino-1-phenyl-1, 3-propanediol and (R)- and (S)-1-phenylethylamine as resolving agents to yield (R)- and (S)-MSA with optical purities of 100%. In addition, the racemic structures of 1-propylammonium and 1-butylammonium salts of (RS)-MSA were examined based on melting point, solubility, infrared spectra, and binary and ternary phase diagrams, with the aim of optical resolution by preferential crystallization of (RS)-MSA. Results indicated that the 1-butylammonium salt of (RS)-MSA [(RS)-BA salt] exists as a conglomerate and that the 1-propylammonium salt forms a racemic compound. Optical resolution by preferential crystallization of (RS)-BA salt yielded (R)- and (S)-BA salts with optical purities of over 90%. The (R)- and (S)-MSA obtained by optical resolution were condensed with (R)- and (S)- 2-amino-3-chloropropanoic acid hydrochlorides to give (2R, 1'R)-, (2S, 1'S)-, (2R, 1'S)-, and (2S, 1'R)-ADC. In addition, these stereoisomers were also synthesized from D- and L-cysteine and optically active bromosuccinic acid.
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  • Marcin DRAMINSKI, Krzysztof TURSKI, Yuji TATEOKA, Toshiyuki KIMURA, Ka ...
    1998 Volume 46 Issue 9 Pages 1370-1373
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Twenty four thiouracil derivatives, including N3-allyl- (19) and N1-allyl-2-thiouracil (20) were synthesized and their pharmacological effects [sedative-hypnotic activity (loss of righting reflex and spontaneous activity), convulsant activity, effect on pentobarbital (PB)-induced sleep and mortality] were evaluated in mice at doses of 320 mg/kg, i.p. and 2 μmol/mouse by intracerebroventricular (i.c.v.) injections, respectively. N3-Allyl-6-propyl-2-thiouracil (3), N3-allyl-5, 6-dimethyl-2-thiouracil (10), N3-allyl-1, 2, 3, 4, 5, 6, 7, 8, 9-nonahydro-4-oxo-2-thiocyclohepta[d]pyrimidine (16) and N3-allyl-5-methyl-2-thiouracil (18) exhibited sedative-hypnotic activity, whereas N3-allyl-6-ethyl-5-methyl-2-thiouracil (11), N1-allyl-5-methyl-2-thiouracil (21), N1-allyl-1, 2, 3, 4, 5, 6, 7, 8, 9-nonahydro-4-oxo-2-thiocyclohepta[d]pyrimidine (23) and N1-allyl-5, 6-dimethyl-2-thiouracil (24) conversely displayed clonic- and/or tonic-convulsant seizures. N3-Allyl-6-propyl-2-thiouracil (3) and N3-allyl-5-methyl-2-thiouracil (18) decreased spontaneous activity. Other compounds examined were inactive, or only slightly active in the sedative-hypnotic assay even at high doses. Fifteen compounds (1-4, 7, 10, 11, 14-16, 18-21, and 23) significantly prolonged the PB-induced sleeping time. Interestingly, only N1-allyl-5, 6-dimethyl-2-thiouracil (24) shortened the PB-induced sleeping time. These results showed that these thiouracils possessed many different effects such as sedative-hypnotic, anticonvulsant and/or convulsant, and that N3-allyl-5-methly-2-thiouracil (18) and N1-allyl-5, 6-dimethyl-2-thiouracil (24) had the most potent hypnotic activity and antagonistic effect against PB, respectively.
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  • Yoshio OKADA, Masaki TSUKATANI, Hiroaki TAGUCHI, Toshio YOKOI, Sharon ...
    1998 Volume 46 Issue 9 Pages 1374-1382
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    An amino group was introduced to the 3 or 6 position of a pyrazinone ring by cyclization of dipeptidyl chloromethyl ketones. Boc-Tyr-OH was coupled with the amino funciton, followed by removal of the Boc group to give pyrazinone ring-containing tyrosine derivatives. Of the various tyrosine derivatives prepared, 5-methyl-6-β-phenethyl-3-tyrosylaminobutyl-2(1H)-pyrazinone exhibited strong binding to the μ-opioid receptor with a Ki value of 55.8 nM and to the δ-opioid receptor with a Ki value of 2165 nM and with a Kiμ/Kiδ value of 0.026.
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  • Dayuan GAO, Riichi TAWA, Hitoshi MASAKI, Yuri OKANO, Hiromu SAKURAI
    1998 Volume 46 Issue 9 Pages 1383-1387
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Baicalein (5, 6, 7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavonoid, was found to prevent human dermal fibroblast cell damage induced by reactive oxygen species such as hydrogen peroxide (H2O2), tert-butyl hydroperoxide (BuOOH) and superoxide anions (·O-2) in a concentration-dependent manner, and was more effective than the iron chelator, deferoxamine, hydroxyl radical (·OH) scavengers such as dimethyl sulfoxide (DMSO) and ethanol (EtOH), the lipid peroxidation chain blocker, α-tocopherol (Vit. E) and the xanthine oxidase inhibitor, allopurinol. To probe the mechanism of cell defense, the reaction of baicalein with oxygen free radicals was investigated using electron spin resonance (ESR) spectrometry. Baicalein decreased the signal intensities due to the 5, 5-dimethyl-1-pyrroline-N-oxide (DMPO) spin adducts of ·OH, ·O-2 and tert-butyl peroxyl (BUOO·) radicals in a concentration-dependent manner. The IC50 values, which are the 50% inhibition concentrations of baicalein for the free radicals, were 10, 45 and 310 μM, respectively. These results suggested that baicalein possesses free radical scavenging ability which prevents the fibroblast damage induced by these free radical species.
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  • Takashi NAKAMURA, Hiroyuki NISHI, Yoshio KOKUSENYA, Tadashi SATO
    1998 Volume 46 Issue 9 Pages 1388-1392
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    As a method for estimation of the antioxidative activity of methanol extracts of crude drugs, cyclic voltammograms (CV), 1, 1-diphenyl-2-picrylhydrasyl (DPPH) radical scavenging activities, and electrochemical detection (ECD)-HPLC were investigated. From a comparison of results, crude drugs which show oxidative peaks in the low potential region in CV, had strong and rapid radical scavenging activities. A correlation (r2=0.76) between DPPH radical scavenging ability and total peak area detected by ECD-HPLC, was obtained. The ECD-HPLC method is therefore useful for evaluation of antioxidative activities, as well as a separational analysis method for antioxidative ingredients.
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  • Tenji KONISHI, Yasuhiro FUJIWARA, Takao KONOSHIMA, Shiu KIYOSAWA
    1998 Volume 46 Issue 9 Pages 1393-1398
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Five new labdane-type diterpenes were isolated from the resinous wood of Excoecaria agallocha. The structures of these compounds were established as ent-13-epi-8, 13-epoxy-2-hydroxylabda-1, 14-dien-3-one (1), ent-13-epi-8, 13-epoxy-14S, 15-dohydroxylabdan-3-one (2), ent-13-epi-8, 13-epoxy-2, 3-secolabd-14-ene-2, 3-dioic acid (3), ent-13-epi-8, 13-epoxy-2, 3-secolabd-14-ene-2, 3-dioic acid 3-methyl ester (4) and ent-13-epi-8, 13-epoxy-2-oxa-3-oxolabd-14-ene-1R-carboxylic acid (5).
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  • Hisashi MATSUDA, Yuhao LI, Toshiyuki MURAKAMI, Narumi MATSUMURA, Johji ...
    1998 Volume 46 Issue 9 Pages 1399-1403
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    We examined the structure-related activity of oleanolic acid glycosides with respect to their inhibitory effect on the increase in serum glucose in oral glucose-loaded rats and their mechanism of action using oleanolic acid 3-O-glucuronide and momordin Ic. Both the 3-O-monodesmoside structure and 28-carboxyl group were confirmed to be essential for such activity, and the 3-O-glucuronide was more potent than 3-O-glucoside. On the other hand, the 28-ester glucoside moiety and 6'-methyl ester of the glucuronide moiety reduced such activity. Oleanolic acid 3-O-glucuronide and momordin Ic, both of which inhibited the increase in serum glucose in oral glucose-loaded rats, did not lower serum glucose in normal or intraperitoneal glucose-loaded rats, or alloxan-in-duced diabetic mice. These glycosides were found to suppress gastric emptying in rats, and also inhibit glucose uptake in the rat small intestine in vitro. These results indicate that oleanolic acid 3-O-glucuronide and momordin Ic, given orally, have neither insulin-like activity nor insulin releasing-activity. They exhibit their hydpoglycemic activity by suppressing the transfer of glucose from the stomach to the small intestine and by inhibiting glucose transport at the brush border of the small intestine.
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  • Junichi KITAJIMA, Chieko OKAMURA, Toru ISHIKAWA, Yasuko TANAKA
    1998 Volume 46 Issue 9 Pages 1404-1407
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Eight new coumarin glycosides were isolated from the methanolic extract of the root and rhizoma of Glehnia littoralis FR. SCHMIDT ex MIQ. (Umbelliferae; "hamabofu" in Japanese). From the results of spectral investigation, they were characterized as glycosides of (S)-peucedanols, (S)-7-O-methylpeucedanols, marmesin and hydroxyimperatorin derivatives, respectively.
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  • Junichi KITAJIMA, Kaoru KIMIZUKA, Yasuko TANAKA
    1998 Volume 46 Issue 9 Pages 1408-1411
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    From the methanolic extract of Ficus pumila L. fruit (Moraceae), two new sterols, (24S)-stigmast-5-ene-3β, 24-diol, (24S)-24-hydroxystigmast-4-en-3-one, two new cycloartane-type triterpenoids, (24RS)-3β-acetoxycycloart-25-en-24-ol, (23Z)-3β-acetoxycycloart-23-en-25-ol and a new euphane-type triterpenoid, (23Z)-3β-acetoxyeupha-7, 23-dien-25-ol were obtained along with known sterols, triterpenoids and a furocoumarin (psoralene).The structures of the new compounds were determined by spectral methods.
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  • Manabu UDAYAMA, Masafumi OHKAWA, Naotoshi YOSHIDA, Junei KINJO, Toshih ...
    1998 Volume 46 Issue 9 Pages 1412-1415
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Three new saponins, named palustrosides I, II and III, together with azukisaponins, II, V and soyasapogenol B monoglucuronide, were isolated from the aerial parts of Lathylus palustris L. var. pilosus LEDEB. The structures of palustrosides I, II and III were identified as 3-O-β-D-glucopyranosyl-(1→2)-β-D-glucuronopyranosides of soyasapogenol E, abrisapogenol E, and bredemolic acid 28-O-β-D-glucopyranoside, respectively, by spectroscopic and chemical methods. As part of our studies on hepatoprotective drugs, we also examined the hepatoprotective effects of these saponins towards immunologically induced liver injury in primary cultured rat hepatocytes. The activity of the disaccharide group was greater than that of the trisaccharide group. This information regarding the structure-activity relationships substantiated previously obtained data. Structure-hepatoprotective relationships for the sapogenol moiety suggested that the hydroxyl group at C-30 reduces the hepatoprotective effect. On the other hand, the carbonyl group at C-22 may be equivalent to a hydroxyl group at C-22 in terms of hepatoprotective action. Oleanolic acid-type saponins also exhibited hepatoprotective action.
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  • Makio SHIBANO, Satoko NAKAMURA, Masami KUBORI, Katsuhiko MINOURA, Genj ...
    1998 Volume 46 Issue 9 Pages 1416-1420
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Two new pyrrolidinyl piperidine alkaloids called broussonetines I and J were isolated from the branches of Broussonetia kazinoki SIEB. (Moraceae). Broussonetines I and J were formulated as (2R)-2-{(1S, 2S)-1, 2-dihydroxy-8-[(2R, 3R, 4R, 5R)-5-(2-hydroxymethyl-3, 4-dihydroxypyrrolidinyl)octyl}-1-acetylpiperidine (1) and (2R)-2-{(1S, 2S)-1, 2-dihydroxy-8-[(2R, 3R, 4R, 5R)-5-(2-hydroxymethyl-3, 4-dihydroxy-1-acetylpyrrolidinyl)]octyl}-1-acetyl-piperidine (2), respectively, by spectroscopic and chemical methods.
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  • Roberto DURO, Carmen ALVAREZ-LORENZO, Consuelo SOUTO, Jose L. GOMEZ-AM ...
    1998 Volume 46 Issue 9 Pages 1421-1427
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Viscometric and cloud-point data for aqueous dispersions of polysorbate 80 and a cellulose ether (one of two varieties of hydroxypropylmethylcellulose (HPMC) or sodium carboxymethylcellulose (NaCMC) which differ regarding molecular mass) indicated the existence of physico-chemical interactions between aggregated surfactant molecules and polymer macromolecules. The implications of these interactions for interfacial adsorption onto pyrantel pamoate particles suspended in various formulations of these polymer-surfactant dispersions were evaluated. Both HPMCs and also the NaCMC of a higher molecular mass were adsorbed, though in smaller amounts than in the absence of the surfactant owing to the weak adsorption activity of the polymer-surfactant associations. No adsorption of polysorbate 80 was detected in these suspensions. By contrast, in suspensions containing the lower molecular mass NaCMC, polysorbate 80 was adsorbed while the polymer apparently was not. The zeta potential and several indicators of physical stability varied among the various suspensions incorporating ionic polymers, and also among those incorporating non-ionic polymers, in a markedly different way from the corresponding formulations which incorporated a polymer or additive alone. Both polymers and alos the polysorbate 80 strongly promoted rapid dissolution of the pyrantel pamoate.
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  • Raja Muhammad HANIF, Ping QINENG, Muo FENZHU
    1998 Volume 46 Issue 9 Pages 1428-1431
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    The tetrahydrogeraniol (THG) derivative, ethyl-(3, 7-dimethyl octyl thio) acetate (EDOTA) was prepared by reacting tetrahydrogeranyl bromide (obtained by reaction of 40% hydrobromic acid and concentrated sulfuric acid) with ethyl 2-mercaptoacetate, while 3, 7-dimethyl octyl propionate (DOP) was synthesized by a common esterification reaction by reacting THG with propionic acid in the presence of cyclohexane and concentrated sulfuric acid. The penetration-enhancing effect of the new enhancers were compared with THG and Azone in vitro using excised rat skin in modified Franz-type diffusion cells. 5-Fluorouracil (5-FU), a hydrophilic drug with poor skin permeability was used as a model permeant. Skin samples were pretreated with pure liquid enhancers for 12 h. 5-FU flux through the control and enhancer-treated skin increased linearly with its concentration in the receptor compartment. EDOTA and DOP interacted with the skin rapidly (<2 h), and the duration of action is at least 24 h. Significant differences were found in the flux values of 5-FU; EDOTA and DOP enhanced the permeability of the drug about 6-fold and 11-fold respectively. Increased partition coefficient and diffusion coefficient values were obtained by these enhancers. The results suggested that the amount of EDOTA and DOP in the skin, especially in the stratum corneum, may be related to their penetration-enhancing effect.
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  • Yousuke MIYAMOTO, Akio RYU, Shinya SUGAWARA, Masaharu MIYAJIMA, Masayu ...
    1998 Volume 46 Issue 9 Pages 1432-1437
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    A computer optimizaiton technique based on surface response methodology was applied to optimize the wet granulation process for designing tablets. Physical properties (mean granule size, granule size distribution, compressibility, granule strength) of a model granule formulation containing ethenzamide were accurately described by a second polynomial equation based on two independent variables (amounts of binder and binder solution). This regression equation also gave a good correlaiton for three physical properties of tablets (disintegration time, compactibility, compression force variance), but the correlation for tablet hardness and weight variation was poor. These results imply that not only the above physical properties of granules but also the rheological behavior and porous structure of granules are closely related to tablet properties. Using an optimization of five tablet properties using the generalized distance funciton, the predicted values of the physical properties of both granules and tablets agreed well with experimental values. This agreement indicates that the computer optimization technique is useful for optimizing the granulation process for designing tablets.
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  • Satoru WATANO, Teruo SUZUKI, Toshinari TAIRA, Kei MIYANAMI
    1998 Volume 46 Issue 9 Pages 1438-1443
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    In a previous paper (Watano et al., J. Soc. Powder Technol. Jpn, 34, 778, 1997), we developed a novel system which could continuousy monitor the electrostatic field strength of powder in a fluidized bed process. This paper reports further study related to the electrostatic characteristics of powder. Two novel achievements are described; one is an improvement of the reliability and accuracy of the sensor, and the other is the mechanism and characteristics of the electrostatic charge for different kinds of powder materials. First, the structure of the sensor extremity has been improved to remove the troubles encountered in the previous sensor. By using a double-walled cylinder, the sensor is devised to tolerate severe vibration, high purge air flow and particle sticking. By increasing the sensitivity, the accuracy of measurement can be increased by approximately five times that of the previous sensor. Secondly, the relationship between electrostatic field strength and the electrical charge of the particles has been investigated using various kinds of powder materials. The sensor shows a good linearlty between two measurements, proving that the electrostatic characteristics of charged particles could be monitored correctly via the electrostatic field strength. The performance of the system has been confirmed in the fluidized bed granulation/drying processes using different kinds of particles. The mechanism of the electrostatic charge for different kinds of powdered materials are also discussed.
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  • Masahiko KUROKAWA, Jun-ichi YAMAMURA, ZhiHong LI, Hitoshi SATO, Nobuyu ...
    1998 Volume 46 Issue 9 Pages 1444-1447
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Gingyo-san is composed of 10 crude drugs and used as a traditional antipyretic medicine for the treatment of the common cold and influenza virus infection. In a murine intranasal influenza infection model, fever produced by the infection has been demonstrated to be reduced by suppressing interferon-induced interleukin (IL)-1α production. Thus, we focused on the serum level of IL-1α which produces such novel antipyretic activity, and evaluated the relationship between defervescence and the suppression of IL-1α production by Gingyo-san in influenza virus-infected mice. Fever was produced in the infected mice 33-44 h after infection. Oral administration of a hot water-extract of Gingyo-san (8.9-12.5 mg/0.25 ml/mouse×3 per day) significantly reduced fever production and suppressed the rise in IL-1α production to the level in uninfected mice. No apparent toxicity by Gingyo-san was observed in infected mice. When the hot water-extract of each 10 of the crude components of Gingyo-san (an unknown amount extracted from 6.25 mg/0.25 ml/mouse×3 per day for Saigae Tataricae Cornu and 3.5 mg/0.25 ml/mouse×3 per day for the other 9) was orally administered to infected mice, 6 showed significant antipyretic activity. Of these 6, Saigae Tataricae Cornu significantly suppressed the rice in IL-1α production to the basal level while the other 5 did not affect serum IL-1α. Thus, of the 10 crude components of Gingyo-san, Saigae Tataricae Cornu simultaneously exhibied antipyretic and IL-1α-regulatory activities. The novel antipyretic action of Gingyo-san may be mainly mediated by Saigae Tataricae Cornu which regulates the elevated serum IL-1α level produced by influenza infection.
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  • Masaya KAWASE, Takaaki SAWADA, Kiyohito YAGI, Tadashi MIZOGUCHI
    1998 Volume 46 Issue 9 Pages 1448-1450
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Copper-ferrite (Cu-ferrite) prepared by the wet formation process was applied to oxidation of 2-methoxyphenol as a model reaction for the removal of pollutants from water. Cu-ferrite was easily recovered with little loss following repeated use of a magnet. The activity of Cu-ferrite was maintained during 3 batch reactions and Cu-ferrite was found to be suitable for the removal of pollutants. The reaction product of both the 2nd and 3rd batches was different from that of the 1st batch. X-Ray diffraction suggested that the structure of Cu-ferrite was changed by leakage of copper ion (Cu2+ ion) from the Cu-ferrite lattice after the 1st batch reaciton. Such a structural change was considered to change the reactivity of Cu-ferrite. It is considered that an improvement in the formation process leads to Cu-ferrite being a more useful and effective catalyst for removing pollutants from water.
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  • Masahiro TADA, Sayako INOUE, Takao MIKI, Shin-ichi ONOGI, Jun-ichi KAM ...
    1998 Volume 46 Issue 9 Pages 1451-1453
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Enantioselective total synthesis of (+)-isoboonein, an iridoid lactone, was accomplished from (-)-dimenthyl bicyclo[2.2.1]hept-5-ene-2, 3-dicarboxylate, which was synthesized by diastereoselective Diels-Alder reaction of dimenthyl fumarate with cyclopentadiene.
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  • Yoji TACHIBANA
    1998 Volume 46 Issue 9 Pages 1454-1458
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Use of 1, 8-diazabicyclo[5.4.0]undec-7-ene (DBU) in boiling xylene was found to be a convenient method for the retro-cycloaddition of adducts of 4-phenyl-1, 2, 4-triazolidine-3, 5-dione (PTAD) with steroidal 5, 7-dienes. This process was applied to the syntheses of ergosta-5, 7, 24(28)-trien-3β-ol and ergosta-5, 7, 22, 24(28)-tetraen-3β-ol.
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  • Tian-Shung WU, Shiow-Chyn HUANG, Pei-Lin WU
    1998 Volume 46 Issue 9 Pages 1459-1461
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Examination of the extract from the root bark of Clausena excavata, yielded four new lactonic carbaczole alkaloids, clausevatine-D (1), -E (2), -F (3), -G (4), as well as the known clausamine-A (5). Their structures were elucidated by spectroscopic analyses.
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  • Noriyuki USAMI, Kiyofumi KOBANA, Hisatoshi YOSHIDA, Toshiyuki KIMURA, ...
    1998 Volume 46 Issue 9 Pages 1462-1467
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Seven halogenated derivatives of Δ9-tetrahydrocannabinol (Δ9-THC, 1) substituted on the aromatic ring at the 2 and/or 4 position, 2 (4)-fluoro- (2), 2, 4-difluoro- (3), 2-chloro- (4), 2-bromo- (5), 2, 4-dibromo- (6), 2-iodo- (7) and 2, 4-diiodo-Δ9-THC (8) were synthesized and pharmacological effects such as catalepsy, anticonvulsant effects, hypothermia, pentobarbital-induced sleep prolongation and locomotor activity evaluated by intracerebroventricular (i.c.v., 25 μg/head) and intravenous (i.v., 5 or 10 mg/kg) injections in mice. The cataleptogenic effects of 2 and 5 were about three-quarters and two-thirds, respectively, compared to those of 1 (i.v.), though other derivatives were much less active (i.c.v. and i.v.) 2 (for clonic seizures) exhibited a significant prolongation of seizure latency induced by pentylenetetrazol (i.v.). Hypothermic effects of monohalogenated derivatives were comparable to 1 when administered by i.v. injection, whereas the effects of dihalogenated derivatives of 1 were attenuated. In contrast, 3 and 8 exhibited a significant hyperthermic effect in mice. In synergy with pentobarbital, 4 and 5 exhibited a significant prolongation of sleeping time by 1.6- and 1.8-fold, respectively, compared with control (32.4±2.5 min), although other derivatives did not affect significantly the sleeping time (i.c.v.). However, by i.v. injection, 2, 4, 5 and 7 significantly prolonged pentobarbital-induced sleeping time and reduced locomotor activity. The sleep prolonging effects of 2, 4 and 7 (10 mg/kg, i.v.) were as potent as that of 1 (5 mg/kg, i.v.). 5 and 7 were the most potent derivatives among the synthetic cannabinoids examined in the present study. These results indicate that halogenation of 1 leads to modification of the pharmacological profile of THC.
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  • Takeshi SUZUKI, Hitoshi NAGAOKA, Yutaka KONDO, Takumi TAKAHASHI, Makot ...
    1998 Volume 46 Issue 9 Pages 1468-1473
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Conversion of the 2-(3-pyridyl)thiazolidine part of 1-(3-phenylpropyl)-4-[2-(3-pyridyl)thiazolidine-4-carbonyl]piperazine (YM461), which is a potent platelet-activating factor (PAF) antagonist, to other rings was performed, and PAF antagonistic activities evaluated. The 2-(3-pyridyl)thiazolidine skeleton, which exists as a mixture of cis and trans diastereomers, played an important role in the potency of PAF antagonism. In this study, new effect skeletons were not uncovered, however, 2-(4-pyridyl)thiazolidine-4-carboxamides (1n and 1z) showed potent PAF antagonistic activities equal to the 3-pyridyl derivatives. From the results obtained for 1a, 1a(S), 1g and 1i, a cis-(2R, 4R)-2-(3-pyridyl)thiazolidine-4-carboxamide was assumed to be the active configuration for PAF antagonism.
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  • Koichi MORI, Miyuki KIDAWARA, Mari ISEKI, Chieko UMEGAKI, Takeo KISHI
    1998 Volume 46 Issue 9 Pages 1474-1476
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    A simple and accurate method for determination of vitamin C (ascorbic acid (AsA) and dehydroascorbic acid (DHA)) using 4, 5-dimethyl-o-phenylenediamine (DMPD) was investigated. It was found that DMPD is a useful fluorescent reagent. The reaction product of DMPD with DHA showed strong and stable fluorescence (Ex; 360 nm, Em; 40 nm). Fluorometric derivatives were extracted with isobutanol or n-butanol. Extraction with isobutanol was superior to that with n-butanol in terms of specificity, since fluorometric derivatives of keto acids were extracted with n-butanol, together with DHA. The fluorescence intensity of DMPD derivatives was absolutely stable in isobutanol for at least 24 h. The sensitivity of determination of vitamin C was improved by removing several non-fluorometric compounds coexisting in the samples. The derivative derived from AsA was easily separated from those of keto acids by an HPLC method. The determination of vitamin C in natural products was thus improved by extraction and the HPLC method.
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  • Shigemi TAZAWA, Tsutomu WARASHINA, Tadataka NORO, Toshio MIYASE
    1998 Volume 46 Issue 9 Pages 1477-1479
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Two new cinnamic acid derivatives along with twenty two known compounds, including five flavoniods, three phenolic compounds, six caffeoylquinic acids and eight cinnamic acid derivatives, were isolated from Brazilian propolis. New compounds were elucidated as (E)-3-(2, 2-dimethyl-3, 4-dihydro-3-hydroxy-8-prenyl-2H-1-benzo pyran-6-yl)-2-propenoic acid and (E)-3-[2, 3-dihydro-2-(1-hydroxy-1-methylethyl)-7-prenyl-benzofuran-5-yl]-2-propenoic acid, on the basis of spectral evidence. Three compounds; dihydrokaempferide, (+)-threo-1-C-guaia-cylglycerol and 3-prenyl 4-(2-methylpropionyloxy)cinnamic acid were isolated from propolis as the first time.
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  • Guillaume GRENIER, Gervais BERUBE, Claude GICQUAUD
    1998 Volume 46 Issue 9 Pages 1480-1483
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    In a previous work we synthesized a class of new antineoplastic drugs by coupling a cisplatin derivative to a triphenylethylene moiety similar to the antiestrogen, tamoxifen. These drugs differ in the number of hydroxy functions on the triphenylethylene rings and in the length of the linking arm.To gain more insight into the cellular mechanism by which these new drugs act on cells, we studied, using differential scanning calorimetry, the effects of these compounds on the phase transition of membrane phospholipid (distearoyl phosphatidyl choline (DSPC)), and correlated these effects to drug cytotoxicity. The drugs without hydroxy function showed the highest cytotoxicity and induced little change on the thermogram of DSPC. Contrarily, the drugs bearing two or three hydroxy groups were less toxic, but induced important modifications of the thermogram.We suggest that the drugs with no hydroxy group enter the membrane, with the triphenylethylene moiety localized deep within the hydrophobic core of the bilayer and do not affect the cooperativity region (C2-C8). In contrast, drugs which bear hydroxy grops on the triphenylethylene rings system perturb the phospholipid molecular arrangement; this may be due either to the additional steric hindrance of te hydroxy functions in the core of the bilayer, or to their hydrophilic effect on the polar head of the lipid.In vitro, the cytotoxic effect of these drugs seems not to be related to their affinity for the estrogen receptor. We suggest that the addition of a triphenylethylene moiety to the platinum(II) complexes increases the hydrophobicity, and consequently the resulting drugs become more permeable to the membrane, particularly the non-hydroxylated triphenylethylene derivatives.
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  • Yasufumi MATSUMURA, Hidemichi FUKAWA, Yoshiyasu TERAO
    1998 Volume 46 Issue 9 Pages 1484-1485
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    (R)-(-)-Muscone was synthesized efficiently by oxidation of 3-(R)-methylcyclopentadecan-1-(RS)-ol, which was obtained by lipase-catalyzed resolution of its diastereomeric mixture.
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  • Atef A. ABDEL-HAFEZ, Meselhy R. MESELHY, Norio NAKAMURA, Masao HATTORI ...
    1998 Volume 46 Issue 9 Pages 1486-1487
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    Seventeen thiopaeonimetabolin-I adducts were obtained as mixtures of diastereoisomers after incubation of paeoniflorin with Lactobacillus brevis in the presence of various thiols. Four compounds, 8-(n-hexylthio)- (8), 8-cyclopentylthio-, 8-(p-tolyl)thio- and 8-benzoylthio- (18) paeonimetabolins, showed 100% protection against pentylenetetrazole-induced convulsions at doses of 0.125, 0.25, or 0.50 mmol/kg, relative to valproic acid (100% protection at 1.5 mmol/kg). For 8 and 18, the principle anticonvulsant activity resided in the (7S)-isomers while (7R)-isomers showed muscle relaxation effects.
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  • Masao TOYOTA, Kyoko KIMURA, Yoshinori ASAKAWA
    1998 Volume 46 Issue 9 Pages 1488-1489
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
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    The ether extract of the Japanese moss Plagiomnium acutum was chromatographed on silica gel and Sephadex LH-20 to give ent-β-cedrene and 3, 7-dolabelladiene-18-ol which has been isolated fro brown algae. To the authors' knowledge, this is the first isolation and identification of sesquiterpenoids from the Musci and the first record of ent-β-cedrene from the plant kingdom.
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  • Osamu NISHIMURA, Takeo MORIYA, Masato SUENAGA, Yoko TANAKA, Takashi IT ...
    1998 Volume 46 Issue 9 Pages 1490-1492
    Published: September 15, 1998
    Released on J-STAGE: March 31, 2008
    JOURNAL FREE ACCESS
    A newly isolated peptide from bovine hypothalamus with prolactin-releasing activity (prolactin-releasing peptide; PrRP) was synthesized by a combination of recombinant DNA technology and a cysteine-specific cyanylation reaction, together with rat and human homologs. The peptides were expressed in the form of fusion proteins with basic fibroblast growth factor mutein, which were purified by heparin-affinity chromatography. The fusion proteins were cleaved at the cysteine residues of the junction site by cyanylation, followed by treatment with ammonia for C-terminal amidation. Purification of the resulting crude peptides was performed using chromatography on a gel-filtration column, a cation-exchange column, and a reversed-phase column. As an example, about 90 mg of bovine PrRP (bPrRP) was obtained from 201 of culture bloth. The purified bPrRP showed full biological activities in binding to its receptor expressed on CHO cells and releasing arachidonic acid metabolite from the same cells, while the C-terminal acid form of bPrRP had little of these activities. These results indicate that the C-terminal amide structure is very important for expressing biological activity. The peptides obtained here might be very useful for studies on their biological significance and roles in vivo.
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