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Volume 34, Issue 1
Displaying 1-50 of 68 articles from this issue
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MASAHIRO NAGAI, SEIJI NAGUMO, SHU-MEI LEE, IKUYO EGUCHI, KEN-ICHI KAWA ...1986 Volume 34 Issue 1 Pages 1-6
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSProtosappanin A (I), C15H12O5, mp 250-251°C, was isolated from the heart-wood of Caesalpinia sappan L. (appan Lignum). It yielded a triacetate (II) on acetylation, and an alcohol (III) on reduction with sodium borohybride. On alkali fusion, I afforded sappanin (IV) along with small amounts of catechol and resorcinol. On the basis of chemical and spectroscopic evidence, the structure of I was established as 3, 10, 11-trihydroxy-7, 8-dihydro-6H-dibenz[b, d]oxocin-7-one. The result of an X-ray crystal structure analysis supported this conclusion. Protosappanin A (I) seems to be the precursor of sappanin, 2, 3', 4, 4'-tetrahydroxybiphenyl, which has been known as an artificial component of Sappan Lignum since 1872, and may be a metabolite of sappanchalcone. A possible biogenetic relationship of sappanchalcone, brazilin, and protosappanin A is discussed. Protosappanin A (I) has a weak sedative effect in mice.View full abstractDownload PDF (692K) -
SACHIKO KONDO, KAZUHISA FUNAKOSHI, SEITARO SAEKI, MASATOMO HAMANA1986 Volume 34 Issue 1 Pages 7-14
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS1-Oxido-4-pyridinediazonium tetrafluoroborate (4-PFB) reacts with olefins (cyclopentene, styrene, ethyl acrylate, indene, cyclohexene, cyclooctene, 1-octene and 1-dodecene) in the presence of tris(dibenzylideneacetone)dipalladium to afford the corresponding alkenylated products (1, 2, 3, 4, 5, 6, 7 and 8) in good yields.1, 2, 3, 5-Oxatriazolo[5, 4-α]pyridinium tetrafluoroborate (2-PFB) also reacts with cyclopentene and styrene to give 2-cyclopentenylpyridine 1-oxides (13 and 14) and (E)-2-(α-styryl)pyridine 1-oxide (15), respectively, in low yields.View full abstractDownload PDF (728K) -
HIROYUKI USUI, TOHRU UEDA1986 Volume 34 Issue 1 Pages 15-23
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2'-Deoxy-8, 2'-ethanoadenosine and its 3'-isomer were synthesized from 2'- and 3'-keto-adenosine derivatives. Treatment of 3', 5'-O-(tetraisopropyldisiloxane-1, 3-dilyl)-2'-ketoadenosine with ethoxycarbonylmethylenetriphenylphosphorane gave the 2'-ethoxycarbonylmethylene derivative, which was reduced to the 2'-hydroxyethyl derivative. This compound was converted to the 2'-iodoethyl-N6, N6-dibenzoyladenosine, which was cyclized by treatment with tri-n-butyltin hybride, then deprotected to furnish 2'-deoxy-8, 2'-ethanoadenosine. Photocyclization of a 2'-phenylthioethyl derivative also gave the ethano-cycloadenosine. 3'-Deoxy-8, 3'-ethanoadenosine was prepared from 2', 5'-di-O-(tert-butyldimethylsilyl)-3'-ketoadenosine via 2', 5'-di-O-acetyl-3'-deoxy-3'-phenylthioethyladenosine by photocyclization. The circular dichroism spectral features of these cycloadenosines are presented.View full abstractDownload PDF (1124K) -
HITOSHI TANAKA, YASUSHI TAKAMURA, MASAYOSHI SHIBATA, KAZUO ITO1986 Volume 34 Issue 1 Pages 24-29
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTwo dibenzazecine derivatives (8 and 9) were readily prepared as a mixture by a photochemical reaction of the bromophenolic compound (6). Reduction of the mixture (8 and 9) with diborane followed by column chromatography on silica gel gave the secondary amine (11), which was converted into the diene derivative (12) by Birch reduction. Treatment of 12 with 5% hydrochloric acid, followed by O-methylation with diazomethane provided the homoerythrina base (1) in 21% yield.On the other hand, the base (1) was also prepared via Birch reduction of the amine (9). The mixture of the amides (8 and 9) was reduced directly with sodium in liquid ammonia and subjected to fractional crystallization to yield 13. On treatment with 5% hydrochloric acid, 13 produced the homoerythrina derivative (14), which was methylated with diazomethane to afford 15. Finally, the homoerythrina base (1) was obtained by reduction of the amide group in 15.View full abstractDownload PDF (750K) -
TOKUNARU HORIE, MASAO TSUKAYAMA, HIROKI KOURAI, YOSHIKAZU NAKAYAMA, MI ...1986 Volume 34 Issue 1 Pages 30-35
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS3', 4'-Bis(benzyloxy)-6-hydroxy-5, 7-dimethoxyflavone (15) was obtained from 6-hydroxy-2, 4-dimethoxy-3-(methoxymethoxy)acetophenone (13) via 6'-hydroxy-2', 4'-dimethoxy-3'-methoxy-methoxy-2-[3, 4-bis(benzyloxy)benzoyl]acetophenone (14). The 5-methoxyl group of the acetate (16) of the flavone (15) was selectively split with about 5% (w/v) anhydrous aluminum chloride in acetonitrile to give 6-acetoxy-3', 4'-bix(benzyloxy)-5-hydroxy-7-methoxyflavone (17). The 5-hydroxyflavone (17) was converted into 3', 4', 5-tris(benzyloxy)-6-hydroxy-8-methoxyflavone (20) by benzylation and hydrolysis. Condensation of the 6-hydroxyflavone (20) with 2, 3, 4, 6-tetra-O-acetyl-α-D-glucosyl bromide, folowed by hydrolysis of the resultant compound afforded the corresponding 6-O-β-D-glucoside (22), which was converted into 3', 4', 5, 6-tetrahydroxy-7-methoxyflavone 6-O-β-D-glucoside (pedaliin) (1) by hydrogenolysis. The process should be useful as a general method for synthesizing 6-O-glucosides of 5, 6-dihydroxy-7-methoxyflavones.View full abstractDownload PDF (734K) -
TSUTOMU OHSAKI, TAKEO KURIKI, TAISEI UEDA, JINSAKU SAKAKIBARA1986 Volume 34 Issue 1 Pages 36-50
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIntramolecular cyclization of caffeidine homologues (2a and 2b) in the presence of ethanolic hydrogen chloride gave 9-oxo-1H-pyrrolo[1, 2-α]purine (4a) and 11-oxo-1H-azepino[1, 2-α]purine (4b) derivatives, both containing a 1, 2, 3, 7-tetrahydro-6H-purin-6-one ring system. Purine ring system compounds, 2-monosubstituted (7) and 2, 2, -disubstituted (8) 1, 2, 3, 7-tetrahydro-6H-purin-6-ones, were synthesized by intermolecular cyclization between caffeidine and aldehydes (5) or ketones (6) in the presence of acid catalysts. Pyrolysis of 4, 7, 8, 9, 9a, 11-hexahydro-1, 4, 9a-trimethyl-5, 11-dioxo-1H, 5H-imidazo[4, 5-f]pyrrolo[2, 1-b][1, 3, 5]-oxadiazocine hydrochloride (9·HCl) derived from a urea derivative (3a) afforded 4a and 1, 4-dimethyl-4, 5-dihydro-5, 7-dioxo-1H, 7H-imidazo[4, 5-d][1, 3]oxazine (11). Many of these compounds (4, 7 and 8) showed relaxing activity against KCl-induced contraction of arterial strips isolated from the rabbit mesenterium, and potent activity was observed in the case of 71.View full abstractDownload PDF (1139K) -
SEIICHI UESUGI, HIROTSUGU MIYASHIRO, KEN-ICHI TOMITA, MORIO IKEHARA1986 Volume 34 Issue 1 Pages 51-60
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn order to elucidate the effects of cytosine methylation on deoxyribonucleic acid (DNA) conformation, three self-complementary deoxyribodecanucleotides, d(ATACGCGTAT), d(ATACGm5CGTAT) and d(ATAm5CGm5 CGTAT), were synthesized by a modified phosphotriester method and their conformational properties were examined by ultraviolet (UV) and circular dichroism (CD) spectroscopy. The two modified decamers were completely resistant to restriction endonuclease MluI, whose recognition sequence is ACGCGT, while the unmodified decamer was completely cleaved by the enzyme. All the decamers were assumed to exist as a B-form duplex in 0.1 M NaCl. The UV-temperature profiles suggested that the modified decamer duplexes have slightly higher stability to thermal perturbation but their melting processes are significantly less cooperative, as compared to the case of the unmodified decamer. All three decamers showed similar CD spectra under various salt conditions, including 4M NaCl and 6M CsF. However, substantial differences in CD spectra were observed in 8M NaClO4 at -20°C. Both modified decamers were assumed to exist as a Z-form duplex under these extreme conditions, and they showed similar UV and CD-temperature profiles which were quite different from those of the unmodified decamer.View full abstractDownload PDF (1039K) -
GEN-ICHIRO NONAKA, FUMIO HASHIMOTO, ITSUO NISHIOKA1986 Volume 34 Issue 1 Pages 61-65
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA chemical examination of black tea polyphenols had led to the isolation of three new red pigments, spitheaflagallin 3-O-gallate (1), epitheaflagallin (2) and theaflagallin (3), together with the known theaflavins 4-7. The structures of the theaflagallins 1-3 have been determined on the basis of spectroscopic and chemical data as unusual benzotropolones formed by oxidative condensation of gallic acid and so-called gallocatechins.View full abstractDownload PDF (627K) -
HIROSHI HARA, AKIRA TSUNASHIMA, HIROSHI SHINOKI, TOSHIFUMI AKIBA, OSAM ...1986 Volume 34 Issue 1 Pages 66-70
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTreatment with acetic anhydride-conc. sulufuric acid of o-quinol acetates (7, 11, 18, 19, 20, 28 and 34), which were derived from the corresponding 6-hydroxy-7-methoxytetrahydroisoquinolines (6, 12, 15, 16, 17, 27 and 31), gave the 5, 6-diacetates (8, 13, 21, 22, 23, 29 and 33, respectively). The diacetates were transformed into the corresponding 5, 6, 7-trimethoxytetrahydroisoquinolines (10, 14, 24, 25, 26, 30 and 32) by hydrolysis and subsequent methylation.View full abstractDownload PDF (583K) -
MASATOSHI YAMATO, HIROKAZU YOSHIDA, KIMIO IKEZAWA, YOSHIE KOHASHI1986 Volume 34 Issue 1 Pages 71-76
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSRing contraction of 6-ethoxycarbonyl-4, 5, 7-trihydroxycoumarin (7) to a 3(2H)-benzofuranone (13) was achieved. Compound 13 was utilized in a synthesis of a griseofulvin analogue (1b) with an ethoxycarbonyl group at the 5 position. However, 1b was found to be inactive in a test of fungicidal activity.View full abstractDownload PDF (674K) -
ETSUJI YAMANAKA, MAYUMI NARUSHIMA, KUNIE(nee NAGASHIMA) INUKAI, SHIN-I ...1986 Volume 34 Issue 1 Pages 77-81
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSConvenient syntheses of 1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo[2, 3-α]quinolizine derivatives (4a, b) and a relatd unsaturated lactam (14) are described. The condensation of tryptamine (1) with 8a, b (prepared from 7a, b by decarboethoxylation), followed by treatment with alkali gave the lactams (4a, b), respectively. The stereochemistry of 4b was determined by conversion to the known cis- and trans-compounds (5b). The condensation of 1 with the sulfenylated ester (10), which was prepared in two ways, followed by treatment with alkali gave the lactams (12a, b). Oxidation of 12a, b with m-chloroperbenzoic acid gave the sulfoxides (13) which were heated at 50°C to give the lactams (14, 15) and the pyridone (16).View full abstractDownload PDF (699K) -
YASUAKI HIRAI, SHUICHI SANADA, YOSHITERU IDA, JUNZO SHOJI1986 Volume 34 Issue 1 Pages 82-87
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe constituents of the leaves, stems and underground parts of Chamaerops humilis L. and Trachycarpus wagnerianus BECC. (Palmae) have been investigated. We isolated and identified methyl proto-dioscin and methyl proto-Pb from the stems, dioscin, Pb, methyl proto-dioscin, methyl proto-Pb and methyl proto-rhapissaponin from the underground parts, and tricin 7-O-rutinoside and methyl proto-Pb from the leaves of C. humilis L. On the other hand, we isolated and identified methyl proto-dioscin and pseudoproto-dioscin from the stems, Pb, Tg, methyl proto-Pb and pseudoproto-Pb from the underground parts, and glucoluteolin, scolymoside, methyl proto-Pb and pseudoproto-Pb from the leaves of T. wagnerianus BECC. This is the first report of the isolation of tricin 7-O-β-rutinoside, Tg and pseudodiosgenin oligosides from Palmae plants, and also the first discovery of pseudosteroidal saponin from natural sources.View full abstractDownload PDF (773K) -
HARUHIRO FUJIMOTO, KUMIKO SUZUKI, HIDEMI HAGIWARA, MIKIO YAMAZAKI1986 Volume 34 Issue 1 Pages 88-99
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe structures of hebevinosides I, II, III, IV, and V, new metabolites from a poisonous mushroom, Hebeloma vinosophyllum, were deduced to be 3β, 16β-dihydroxy-7β-methoxycucurbita-5, 24-diene-3-O-β-D-xylopyranoside-16-O-(6-O-acetyl)-β-D-glucopyranoside (1), 3β, 7β, 16β-trihydroxycucurbita-5, 24-diene-3-O-(4-O-acetyl)-β-D-xylopyranoside-16-O-(6-O-acetyl)-β-D-glucopyranoside (22), 3β, 7β, 16β-trihydroxycucurbita-5, 24-diene-3-O-β-D-xylopyranoside-16-O-(6-O-acetyl)-β-D-glucopyranoside (24), 3β, 16β-dihydroxy-7βmethoxycucurbita-5, 24-diene-3-O-β-D-xylopyranoside (16), and 3β, 16β-dihydroxy-7β-methoxycucurbita-5, 24-diene-3-O-(4-O-acetyl)-β-D-xylopyranoside-16-O-(6-O-acetyl)-β-D-glucopyranoside (27), respectively, on the basis of chemical and spectral evidence, as well as the structure determination by X-ray crystallographic analysis of ethoxyhebevinogenin (20), obtained by enzymatic hydrolysis of 16. Hebevinosides I, II, III, and V were proved to be toxic principles of this mushroom.View full abstractDownload PDF (1240K) -
TSUTOMU NAKANISHI, AKIRA INADA, DAVID LAVIE1986 Volume 34 Issue 1 Pages 100-104
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new tirucallane-type triterpenoid derivative, which we have named lipomelianol, has been obtained, together with a known triterpenoid, melianone (4), from fruits of Melia loosendan SIEB. et ZUCC. Lipomelianol was established to be a mixture of the 3-O-stearate, palmitate, myristate, and laurate (ca. 3 : 35 : 32 : 30) of melianol (3), as shown by formula 1, based on chemical, physico-chemical, and spectral evidence. High-resolution 13C-nuclear magnetic resonance data for 1, 3, and 4 are also reported.View full abstractDownload PDF (618K) -
YOSHIYASU TERAO, YUKA YASUMOTO, KIYOSHI IKEDA, MINORU SEKIYA1986 Volume 34 Issue 1 Pages 105-108
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIt has been found that tetracyclic hexahydro-1, 3, 5-triazines react with arenethiols to give 2-arylthio-substituted alicyclic amines. This new reaction provides a useful method for the introduction of arylthio groups at the α-position of alicyclic amines. The reaction with thioglycolate gives bicyclic thiazolidine derivatives, some reactions of which are also described.View full abstractDownload PDF (471K) -
AKIO OHSAWA, HEIHACHIRO ARAI, HIDEFUMI OHNISHI, TERUMITSU KAIHOH, KENT ...1986 Volume 34 Issue 1 Pages 109-114
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSN-Oxidation of substituted 1, 2, 3-triazines afforded the 1- and/or 2-oxides. The molecular structure of 4, 5, 6-triphenyl-1, 2, 3-triazine 2-oxide was studied crystallographically.View full abstractDownload PDF (674K) -
KOJI IUCHI, MASAHIRO NITTA, KEIZO ITO, YASUO MORIMOTO, GORO TSUKAMOTO1986 Volume 34 Issue 1 Pages 115-120
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFive CCK (cholecystokinin)-like peptides [CCK(27-32)amide, CCK-6, CCK-7, Boc-CCK-7 and nonsulfated CCK-7] were prepared by stepwise condensation in combination with fragment condensation by the active ester procedure. The analgesic effects of these CCK-like peptides were measured in the writhing test. The ED50 value of CCK-7 was 1500 nmol/kg (1.8 mg/kg). Boc-CCK-7 appeared to reduce writhing between doses of 1 and 8 mg/kg but did not show a dose-dependent response. Other synthesic peptides produced no response even at a dose of 8 mg/kg. Our results suggested that CCK-7 is one of the shortest CCK-fragments that can retain the analgesic effect.View full abstractDownload PDF (773K) -
IKUO KATSUMI, HIDEO KONDO, KATSUJI YAMASHITA, TAKAYOSHI HIDAKA, KAZUNO ...1986 Volume 34 Issue 1 Pages 121-129
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTwo α-benzylidene-γ-butyrolactones, α-(3, 5-dimethyl-4-hydroxybenzylidene)-γ-butyrolactone and α-(3, 5-di-tert-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), were found to have platelet aggregation inhibitory activity; the latter also had potent antiinflammatory activity and inhibited not only prostaglandin synthetase (PGS) but also 5-lipoxygenase. Further α-benzylidene-γ-butyrolactones were synthesized, and tested for antiinflammatory activity in carrageenin-induced rat paw edema assay (CPE) and for PGS inhibitory activity. It was found that the structural combination of a tert-butyl group at the 3 position, an alkyl group at the 5 position and an oxygen atom at the Δ position in α-benzylidene-γ-butyrolactone is necessary for antiinflammatory activity, and that rather broad structural variation is possible for inhibitors of PGS. The structural requirements for antiinflammatory activity in the CPE assay also seem to be partial requirements for inhibitory activity against PGS.View full abstractDownload PDF (949K) -
YUTAKA MASUOKA, TSUNEHIKO(deceased) ASAKO, GIICHI GOTO, SHUNSAKU NOGUC ...1986 Volume 34 Issue 1 Pages 130-139
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe intramolecular Michael addition of 4-(2-hydroxyanilino)-2-butenoates (3), -2-buteno-nitrile, and their 3-phenyl analogs (8) gave 3, 4-dihydro-2H-1, 4-benzoxazine-2-acetates (4), -2-acetonitrile (6), and their 3-phenyl analogs (9), respectively, in good yields. In addition, 3, 4-dihydro-3-oxo-2H-1, 4-benzoxazine-2-acetates (13) and 3, 4-dihydro-2-(p-nitrobenzyl)-2H-1, 4-benzoxazine (16) were synthesized from 2-hydroxyanilines (1) by the addition reaction of fumaric acid chloride monoester (11) and p-nitrocinnamyl bromide (14), respectively. In order to examine the biological activities of the 2H-1, 4-benzoxazine analogs, 2-(2-dialkylaminoethyl)-(18) and 2-(2, 2-diphenylethyl)-2H-1, 4-benzoxazines (19, 20) were prepared.Among the compounds synthesized, 4b and 19a showed considerable anxiolytic activity in the conflict test in rats, while the oxalates of 18a-c showed potent anticonvulsant activity.View full abstractDownload PDF (898K) -
YUTAKA MASUOKA, TSUNEHIKO(deceased) ASAKO, GIICHI GOTO, SHUNSAKU NOGUC ...1986 Volume 34 Issue 1 Pages 140-149
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS1, 2, 3, 5-Tetrahydro-2-oxo-4, 1-benzoxazepine-3-acetates (5, 13, 16), 2, 3, 5, 6-tetrahydro-2-oxo-1H-4, 1-benzoazocine-3-acetates (21), and 1, 2, 3, 5, 6, 7-hexahydro-2-oxo-4, 1-benzoxazonine-3-acetate (25) were obtained from 3-[[2-(ω-hydroxyalkyl)phenyl]carbamoyl]acrylates (4, 12, 15, 20, 24) by the intramolecular Michael addition previously developed for the synthesis of 3, 4-dihydro-2H-1, 4-benzoxazine-2-acetates. In the case of 5-phenyl-3-oxo-4, 1-benzoxazepine-3-acetates (13), the 3, 5-cis and 3, 5-trans isomers were obtained in a ratio of 1 : 1. Under basic conditions, each isomer was equilibrated to a mixture of cis- and trans-13 in a ratio of 1 : 3. A deuterium exchange experiment revealed that the isomerization proceeded through the retro-Michael reaction. The stereochemistry of trans-13e was confirmed by X-ray analysis.Among the compounds (13) synthesized, N-isopropyl (cis-13c), N-benzyl (cis- and trans-13e) and N-phenethyl (cis-13f) derivatives showed considerable anxiolytic activity in the conflict test in rats.View full abstractDownload PDF (896K) -
5-Fluorouracil Derivatives. X. : Synthesis and Antitumor Activities of α-Alkoxyalkyl-5-fluorouracilsSHOICHIRO OZAKI, YUTAKA WATANABE, TOMONORI HOSHIKO, TOSHIO NAGASE, TOM ...1986 Volume 34 Issue 1 Pages 150-157
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSWith the aim of diminishing the toxicity of 5-fluorouracil (1) and obtaining biologically active derivatives of 1 suitable for oral administration, α-alkoxyalkyl groups were introduced at the 1-, 3-and 1, 3-positions of 1. Alkoxyalkylation can be effected by four methods : (i) reaction of 1-alkoxyalkyl chloride (2) with 1, (ii) reaction of acetal with 2, 4-bis (trimethylsiloxy)-5-fluoropy-rimidine, (iii) addition reaction of α-unsaturated ether with 1, (iv) aminolysis of 1-alkylthio-carbonyl-3-(1-alkoxyalkyl)-5-fluorouracil. The toxicity of the products was less than that of 1, and some of these compounds showed moderate antitumor activity against L-1210 leukemia.View full abstractDownload PDF (723K) -
MASAO HATTORI, YOSHIYUKI ENDO, SACHIKO TAKEBE, KYOICHI KOBASHI, NOBORU ...1986 Volume 34 Issue 1 Pages 158-167
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSAfter single oral administration of [ring-14C]magnolol, a central nervous system-depressive, muscle-relaxant and bactericidal principle of Magnoliae Cortex to rats, the blood levels of radioactivity showed two peaks at 15 min and 8 h, suggesting an enterohepatic circulation of magnolol and its metabolites. The radioactivity was distributed mostly in the gastrointestinal tract and liver, and next in the kidney, pancreas and lung. A major metabolite excreted in the bile was [ring-14C]magnolol-2-O-glucuronide.After oral and intraperitoneal administration of [ring-14C]magnolol, most of the radioactivity was eliminated into the feces and urine within the first 12 h in either case. The oral dose was recovered to a greater extent from the feces (72% of the administered radioactivity) than from the urine (7.4%) in 144 h, and the intraperitoneal dose was similarly recovered from the feces (67%) and from the urine (12%).On repeated oral administration of cold and [ring-14C]magnolol, the composition of the fecal metabolites significantly changed, and tetrahydromagnolol, 5-((E)-1-propenyl)-5'-propyl-2, 2'-dihydroxybiphenyl, 5-allyl-5'-propyl-2, 2'-dihydroxybiphenyl, isomagnolol and 5-allyl-5'-((E)-1-propenyl)-2, 2'-dihydroxybiphenyl were detected.View full abstractDownload PDF (972K) -
KENICHIRO NAKASHIMA, SHIN'ICHI NAKATSUJI, SHUZO AKIYAMA, TAKEHIRO KANE ...1986 Volume 34 Issue 1 Pages 168-173
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTo characterize "crowned" 4-(2, 4-dinitrophenylazo)phenol (CDPA), the acid dissociation constant (pKa) was measured together with those of related compounds. The complexation behavior of CDPA was examined in various nonaqueous solvent systems, and it was found that in the CHCl3-MeOH-triethylamine (TEA) system, the ionic radii of the alkali and alkaline earth metal ions are linearly correlated both with the wave numbers of the absorption maxima and with the molar absorptivities of the resulting complexes except for Be(II). The molar ratios of metal ions to CDPA in the complexes were determined by means of the continuous variation method. Next, the complexation of CDPA with Li(I) was fully examined in another solvent system (CHCl3-dimethyl sulfoxide-TEA) and a sensitive colorimetric assay method for Li(I) was established in the range of 25-250 ppb of Li(I). This method was applied to the analysis of a commercial pharmaceutical preparation, lithium carbonate (tablet).View full abstractDownload PDF (606K) -
MITSUAKI SANO, MASASHI ABE, KYOJI YOSHINO, TOSHIKI MATSUURA, TOSHIAKI ...1986 Volume 34 Issue 1 Pages 174-178
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA convenient method to determine the antioxidative activities of chemicals by using α-methylindole (MI) reagent in conjunction with high-performance thin-layer chromatography (HPTLC) is described. One μl of a mixture of 2% linolenic acid and test sample in ethanol solution was applied to a thin-layer chromatographic (TLC) plate and peroxidized at 80°C for 20 min. The lipid peroxides which were produced from the linolenic acid on TLC were detected as pink spots by spraying MI reagent and were measured at 557 nm with a TLC densitometer.When the test samples showed intrinsic colors interfering with this measurement, they were separated by developing the TLC plate after spraying MI reagent. The antioxidative activity of the test sample is expressed as the amount required to inhibit the peroxidation of linolenic acid by 50%.This method is very simple and rapid. It may be useful when the test samples are available only in small amounts.View full abstractDownload PDF (531K) -
KAZUTAKE SHIMADA, FUMING XIE, TOSHIO NAMBARA1986 Volume 34 Issue 1 Pages 179-187
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe A-ring monoglucuronides and monosulfates of 4-hydroxyesteriol were synthesized from 4-hydroxyestriol 16, 17-diacetate by means of the Koenigs-Knorr reaction with methyl α-acetobromoglucuronate and sulfation with sulfur trioxide-pyridine complex, respectively. The conjugated positions of these compounds were unequivocally elucidated by leading the products to guaiacol estrogens. The D-ring monoglucuronides and monosulfates of 4-hydroxyestriol were also obtained from 4-hydroxyestriol 3, 4-dibenzyl ether by glucuronidation and sulfation followed by hydrogenolysis, respectively. The conjugated positions were established on the basis of spectral data of derivatives. The preparation of 4-hydroxyestradiol 17-conjugates is also described.View full abstractDownload PDF (1153K) -
MICHIKO MIYAHARA, SHOKO SUEYOSHI, SHOZO KAMIYA1986 Volume 34 Issue 1 Pages 188-193
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThree structurally typical N-nitrosoureas showed different life-prolonging activities on animals bearing ascites hepatoma AH13 and lymphoid leukemia L1210 cells. 1-(2-Chloroethyl)-1-nitroso-3-(3-pyridylmethyl)urea N-oxide (CNPyUO) was highly effective against both AH13 and L1210, 1, 3-diphenyl-1-nitrosourea (DPhNU) was effective against AH13 but not against L1210, and 1-methyl-1-nitrosourea (MNU) was effective against L1210 but not against AH13.The cytostatic and deoxyribonucleic acid (DNA)-damaging activities of these N-nitrosoureas on both tumor cells in vivo or in vivo were studied. In the case of CNPyUO treatment in vivo, the formation of cross-linked DNA caused cell death of both tumor cells at 72h after treatment. DPhNU treatment rapidly caused scission of single-stranded DNA of the tumor cells, leading to cell death. MNU treatment caused scission of single-stranded DNA of both cells but showed cytostatic action only on L1210 cells.View full abstractDownload PDF (608K) -
SHUICHI MIYAURA, HIDEO ISONO1986 Volume 34 Issue 1 Pages 194-205
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSMultiple forms and properties of glutathione S-transferase were investigated by using the liver from individual male or female rabbits. Most of the activity toward 1-chloro-2, 4-dinitrobenzene (CDNB) in the crude extract passed through a diethylaminoethyl (DEAE)-cellulose column. On carboxymethyl (CM)-cellulose chromatography, the flow-through fraction was resolved into at least four activity peaks which were designated as R1, R2, R3 and R4 in order of elution. The content of each component varied among the individual rabbit livers examined. The main components, R2 and R3, were further purified to homogeneity as judged by sodium deodecyl sulfate (SDS)/polyacrylamide-gel electrophoresis. R3 contained two forms, whcih were named R3a and R3b in order of elution from a hydroxylapatite column. R2, R3a and R3b each had a molecular weight of approximately 51000 as estimated by gel filtration. R2 and R3b appeared to be homodimers consisting of subunits of apparently different size (R2, Y2 : 25000; R3b, Y3 : 2650). On the other hand, R3a was a heterodimer composed of subunits with molecular weights of 24500 (Y1) and 26500 (Y3). The molecular weight of the subunit of R3b was identical with that of Y3. These enzymes showed the highest activity toward CDNB and much lower activities toward the other substrates tested, and the substrate specificities of all the enzymes were roughly similar to each other.Our highly purified enzyme forms were compared with rat hepatic glutathione S-transferases with regard to substrate specificity, subunit species, kinetic parameters, isoelectric point and amino acid composition.View full abstractDownload PDF (1313K) -
MASAHIKO KISHI, KAZUYASU NAKAYA, YASUHARU NAKAMURA1986 Volume 34 Issue 1 Pages 206-213
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSWhen AH-66 hepatoma ascites cells were incubated in an isotonic saline solution (PBS) at 0°C for 1 h, material composed of approximately 90-95% protein and 5% carbohydrate was released without significantly affecting the viability of the cells. The material released into PBS contained no Na+, K+-adenosine triphosphatase and very low levels of phospholipid, cholesterol, and sialic acid, indicating the absence of contamination by fragments of the plasma membranes. The protein in the released material amounted to as much as approximately 2% of the total cell proteins and most of the protein components of the released material were identical with those of the plasma membranes as analyzed by sodium dodecyl sulfate-gel electrophoresis. The amino acid compositions of proteins of the released material were also very similar to those of the plasma membrane proteins. In contrast to the plasma membranes, however, the released material lacked periodate-Schiff-stainable glycoproteins and proteins with molecular weights larger than about 120000. The absence of sialic acid indicates that the carbohydrate chains, if any, of the proteins in the released material are incomplete. The surface structure of AH-66 cells implied by these results contrasts with that of erythrocyte membranes.View full abstractDownload PDF (917K) -
KUNIHIKO MORITA, YUKIO HAYASHI, TAKESHI ONO, HARUMI SHIMAKAWA1986 Volume 34 Issue 1 Pages 214-220
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe inhibitory and inducing actions of feprazone (FZ), an anti-inflammatory agent, on testosterone hydroxylations in the mouse hepatic microsomal mixed-function oxidase system were compared with those of phenylbutazone (PZ).As regards inhibitory effects, testosterone hydroxylations were competitively inhibited by addition of FZ and PZ in vitro. No significant difference was found between FZ and PZ in inhibitory potency for 6β- and for 16α-hydroxylations, but the inhibitory effect FZ on 7α-hydroxylation was stronger than that of PZ. However, the three hydroxylations were noncompetitively inhibited in microsomes from mice treated with each agent.As regards the inducing action, only 6β-hydroxylase activity was increased following continuous administration of low doses (75 mg/kg) of FZ and of PZ; in addition, 16α-hydroxylase activity was also increased following continuous administration of high doses (150 mg/kg) of these drugs. 7α-Hydroxylase activity, however, was not significantly affected by either low or high doses. We also found that the patterns and the extents of induction of the three hydroxylase activities by FZ and PZ were different from those by phenobarbital or β-naphthoflavone.These results indicate that FZ and PZ have essentially identical inducing effects, whereas FZ exhibits a greater inhibitory effect than PZ on the activity of certain P-450 isozymes such as 7α-hydroxylase in the mouse mixed-function oxidase system.View full abstractDownload PDF (709K) -
MITSUAKI SANO, YASUHARU TAKENAKA, REIKO KOJIMA, SHIN-ICHI SAITO, ISAO ...1986 Volume 34 Issue 1 Pages 221-228
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe effect of water extracts of Pu-Erh tea (products of Yunnan district, China, preserved for 2 or 20 years) and of green tea (products of Shizuoka prefecture, Japan) on lipid level, tissue weight, lipoprotein lipase (LPL) and adrenalin-induced lipolytic (AIL) activity in rats were examined. Female Wistar rats (8 weeks old) were fed a diet containing 1% cholesterol and given the above tea extracts in drinking water for 8 or 16 weeks ad libitum. The levels of plasma cholesterol ester in rats given Pu-Erh tea or green tea were significantly lower than those of control rats after 6-8 weeks, though the difference became smallar after 10 weeks. The triglyceride (TG) level in plasma was also low in rats given Pu-Erh tea for 16 weeks. This effect on TG was not observed in the case of green tea. Among 6 organs or tissues of rats examined, the weight of abdominal adipose tissue was significantly lower in rat fed Pu-Erh tea for 16 weeks. The LPL activity in abdominal adipose tissue tended to be low (though not statistically significant), while the activity of AIL was significantly elevated in rats given Pu-Erh tea for 8 or 16 weeks. A negative correlation was observed between AIL activity and the ratio of adipose tissue/body weight. These data suggest that the successive administration of Pu-Erh tea could stimulate the degradation of TG in adipose tissue and thereby decrease its weight.View full abstractDownload PDF (801K) -
BUN-ICHIRO ONO, NAOKO ANDOU, MANLI WENG, KEZONG TONG1986 Volume 34 Issue 1 Pages 229-234
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSSaccharomyces cerevisiae strains defective in cysteine biosynthesis were more sensitive to chromate than their corresponding isogenic prototrophic strains. Chromate sensitivity of the cysteine-dependent strains was reduced when L-cysteine was added to the growth medium. The effect of L-cysteine on chromate sensitivity was, however, not specific to the cysteine-dependent strains but was general to all strains tested. That is, addition of L-cysteine to the growth medium containing chromate caused an increase of colony-forming ability of chromate-sensitive, normal and chromate-resistant strains. It was also shown that L-cysteine nonbiologically consumed chromate. From these results, we conclude that cysteine plays an essential role in defence of cells against chromate. We contend that cysteine chemically reduces toxic hexavalent chromium to less toxic trivalent chromium; detoxication of chromate by this mechanism takes place intracellularly as well as extracellularly.View full abstractDownload PDF (665K) -
YOSHIFUMI MATSUDA, YUKIO FUJIMOTO, SUMIYUKI AKIHAMA, ATSUSHI MIYASHITA1986 Volume 34 Issue 1 Pages 235-240
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSHuman urinary arginine esterase-2 (HUAE-2) was purified to homogeneity mainly by chromatographic methods. About 2950-fold purification was achieved, with yield of 30% of the initial N-α-tosyl-L-arginine methyl ester (Tos-Arg-Me) hydrolyzing activity. The specific activity of the finally purified HUAE-2 was 2.07 μmol/min/A280 for Tos-Arg-Me. The esterolytic and amidolytic actions of this enzyme showed broad specificities for arginine and lysine derivatives as substrates, and the substrate specificity of this enzyme was clearly different from that of partially purified human urinary arginine esterase-1 (HUAE-1). Aprotinin strongly suppressed the Val-Leu-Arg-pNA amidolytic activity of HUAE-2, while ovomucoid trypsin inhibitor and lima bean trypsin inhibitor were less effective. The isoelectric point (pI value) and optimum pH of this enzyme were determined to be pI 4.5 and pH 8.5, respectively.View full abstractDownload PDF (638K) -
KIYOMI KIKUGAWA, MASUMI ARAI1986 Volume 34 Issue 1 Pages 241-249
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIt is known that hemoglobin A [Hb A (α2β2)] is cross-linked by reaction with double-headed aspirin [bis (3, 5-dibromosalicyl)fumarate], and the cross-linking site is the β-cleft of the tetramer, the binding site of 2, 3-diphosphoglycerate. Reaction of methemoglobin [metHb (α2+β2+)] with the reagent resulted in the formation of MetHbFu, which was confirmed to be a MetHb tetramer intramolecularly cross-linked at the same site. Unstable valency asymmetrical hybrid hemoglobin [Hb AM (αα+ββ+)], which is assumed to be present in a mixture of Hb A and MetHb, could be fixed as a stable tetramer [HbAMFu] by the cross-linking reaction. The intramolecular cross-links in HbAMFu were at the same β-cleft. It is suggested that MetHb forms the valency asymmetrical hybrid in the presence of Hb A.View full abstractDownload PDF (877K) -
YUTAKA KAWAZOE, ATSUSHI HAKURA, KOHFUKU KOHDA1986 Volume 34 Issue 1 Pages 250-255
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn order to study the mutagenic interaction between two chemicals, the mutation frequencies induced by simultaneous (combined) treatments of Salmonella typhimurium TA100 with two simple alkylating agents were compared with those induced by separate treatments with the two mutagens. The results indicated that etthylations produced by two ethylating agents, N-ethyl-N-nitrosourea (ENU) and ethyl methanesulfonate (EMS) may be recognized as equivalent mutational damage of deoxyribonucleic acid (DNA) by the host cell tested, and that methylation by N-methyl-N-nitrosourea and ethylation by either ENU or EMS may be recognized as partially but not entirely equivalent damage of DNA leading to mutation. In contrast, the isopropylation by N-isopropyl-N-nitrosourea appeared to be independent of either methylation or ethylation in inducing mutation. An analytical method for the classification of the mutagenic interactions as "equivalent" or "independent, " is proposed.View full abstractDownload PDF (655K) -
NAOMI YAMAKAWA, SHINJI SOEDA, HIROSHI SHIMENO, ATSUO NAGAMATSU1986 Volume 34 Issue 1 Pages 256-263
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSProline endopeptidase (PEPase) was purified 71800-fold from the soluble fraction of rat liver with a yield of 65.2%. Ammonium sulfate fractionation and chromatographies on diethyl aminoethyl (DEAE)-Sepharose CL-6B, DE-52, blue Sepharose CL-6B, carbobenzoxyglycyl-L-prolyl-AH-Sepharose 4B and Mono-Q were used for the purification of the enzyme. Among the purification procedures, bue Sepharose CL-6B chromatography was the most effective step to eliminate various contaminants. The final enzyme preparation had a high specific activity of 12200 unit/mg protein and showed maximal activity at pH 5.9 toward succinylglycyl-L-proline 4-methylcoumaryl-7-amide (Suc-Gly-Pro-MCA). The Km and Vmax values for Suc-Gly-Pro-MCA were 0.43 mM and 52.0 μmol/min/mg protein, respectively. The apparent molecular weight of rat liver PEPase was estimated to be 68000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and 59000 by gel filtration on TSK-Gel G-4000 SW. The enzyme was extremely sensitive to disopropyl fluorophosphate, but no effect was observed with aprotinin, soybean trypsin inhibitor or ethylenediaminetetraacetate. In addition, the enzyme activity was strongly inhibited by p-chloromercuribenzoate and Hg2+. Elastatinal and 1, 10-phenanthroline also significantly inactivated the enzyme. These results indicate that rat liver PEPase was similar to PEPase purified previously from rat brain, porcine liver and other sources in some enzymatic properties and in molecular nature. The distribution of the enzyme was similar to that of the cytosol marker enzyme, lactate dehydrogenase.View full abstractDownload PDF (839K) -
NAOHITO OHNO, IWAO SUZUKI, TOSHIRO YADOMAE1986 Volume 34 Issue 1 Pages 264-268
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn this paper, carbon-13 nuclear magnetic resonance (13C-NMR) spectra of some edible mushrooms, Grifola frondosa, Lentinus edodes, Flammulina velutipes, Pholiota nameko, Agaricus bisporus, Lyophyllum cinerascens, Lyophyllum aggregatum, and Peziza vesiculosa, as aqueous suspensions were measured and the glucan compositions in these mushrooms were compared. The 13C-NMR spectrum of each native mushroom gave signals attributable to both low and high molecular weight carbohydrates. Low molecular weight carbohydrates were different in each mushroom. As high moelcular weight carbohydrates, all the mushrooms belonging to Basidiomycotina (G. frondosa, L. edodes, F. velutipes, P. nameko, A. bisporus, L. cinerascens, and L. aggregatum) showed β-linked glucan signals. G. frondosa, and P. nameko also showed α-glucan signals. After removal of low molecular weight substances and α-glucans by refluxing with 80% ethanol, dialysis or amylase digestion, all of the spectra were quite similar and showed representative signals at 104, 85, 77, 76, 74, 70, 69, 62 ppm. On the other hand, though P. vesiculosa, a fungus belonging to Ascomycotina, contains antitumor β-glucans, this mushroom showed strong signals attributable to α-glucans and only weak signals attributable to β-glucans. After treatment of G. frondosa with periodate and borohybride, most of the β-glucan signals disappeared. These results suggest that (1) 13C-NMR spectroscopy is applicable to chemotaxonomical examination of fungi, (2) all of the mushrooms belonging to Basidiomycotina contain quite similar glucans, (3) β-signals in these spectra are attributable to periodate-sensitive linkages.View full abstractDownload PDF (635K) -
YOSHIO INOUYE, YASUCHIKA MATSUDA, TADJUDIN NAID, SHIGETETSU ARAI, YASU ...1986 Volume 34 Issue 1 Pages 269-274
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSCreatinine amidohydrolase (creatininase) from Alicaligenes sp. nov. was purified to electrophoretic homogeneity by adsorption on diethylaminoethyl-cellulose, affinity chromatography on creatinyl-AH-Sepharose, gel filtration on Sephadex G-200 and hydroxyapatite chromatography. The molcular weight of the enzyme was estimated to be approximately 160000 by gel filtration on Sephadex G-200 and 80000 by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis, and the enzyme was assumed to consist of two identical subunits. The enzyme showed maximum activity at pH 7-8 and was stable in the pH range of 8-11.5. The enzyme catalyzed interconversion between creatinine and creatine, and the Km values for creatinine and creatine were 60.9 mM and 162 mM, respectively. Though the enzyme was markedly inactivated by ethylenediamine-tetraacetate (EDTA), N-bromosuccinimide, Zn2+, Cu2+, Ni2+ or Co2+, activation of the enzyme was only observed in the presence of Mn2+. Furthermore, the reactivation of EDTA-treated inactive enzyme was observed on the addition of Mn2+ to the reaction mixture.View full abstractDownload PDF (630K) -
YOSHIMITSU SHIMAMORI, YASUHIRO WATANABE, YUKIO FUJIMOTO1986 Volume 34 Issue 1 Pages 275-280
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe substrate specificity of a purified kidney neutral endopeptidase was studied. The endopeptidase hydrolyzed a variety of biologically active peptides, such as angiotensins (angiotensins I, II and III), bradykinins (bradykinin, Lys-bradykinin, Met-Lys-bradykinin and des-9Arg-bradykinin), enkephalins (Leu-enkephalin and Met-enkephalin), neurotensin and substance P, and was found to cleave only the bonds at the amino side of hydrophobic amino acids in the peptides. However, when a hydrophobic amino acid was present at the C-terminus or at the position adjacent to the N-terminus, the bond of the hydrophobic residue was not cleaved. In further studies on the degradation of a series of homo-oligopeptides, the enzyme appeared to hydrolyze those consisting of at least a tetrapeptide unit of hydrophobic amino acids such as Ala and Phe. The specificity of the membrane-bound neutral endopeptidase from rat kidney indicated by these results can be summarized as follows : the enzyme requires at least a tetrapeptide unit for hydrolysis, and cleavage occurs only at the amino side of a hydrophobic amino acid, when one is present at the third position of the tetrapeptide unit.View full abstractDownload PDF (662K) -
NOBUO AOYAGI, HIROYASU OGATA, NAHOKO KANIWA, MASANOBU KOIBUCHI, TOSHIO ...1986 Volume 34 Issue 1 Pages 281-291
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe dissolution of sugar-coated tablets of thiamine disulfide largely depended on the lag time, which was greatly affected by the pH of the medium, and was accelerated by mechanical destructive force. The disintegration time-pH profiles were very similar to the dissolution rate-pH profiles determined by using a disintegration test device. Markedly slow dissolution and disintegration of one of the tablets at pH 7.2 was attributed to the dissolving characteristics of polyvinylacetal-diethylaminoacetate (AEA[○!R]) applied to the tablet as a coating film, and the slow dissolution of another tablet at pH 3-5 was attributed to the use of 2-methyl-5-vinylpyridine-methylacrylate-methacrylic acid copolymer (MPM[○!R]). Six products were tested for bioavailiability. Statistically significant differences were found in bioavailability among the products. Human gastric acidity greatly affected the bioavailability of the tablet that disintegrated poorly at pH 7.2, and the bioavailiability was significantly lower in subjects with low gastric acidity than in those with high gastric acidity. The in vivo parameters of high and low acidity subjects correlated well with the in vitro parameters determined at pH 1.2-5 and pH 5-7.2, respectively.View full abstractDownload PDF (1062K) -
NOBUO AOYAGI, HIROYASU OGATA, NAHOKO KANIWA, MASANOBU KOIBUCHI, TOSHIO ...1986 Volume 34 Issue 1 Pages 292-300
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe bioavailabilities of six brands of thiamine disulfide (TDS) sugar-coated tablets were investigated in male beagle dogs and the correlations with the bioavailabilities in humans and the in vitro dissolution rates were investigated. the volume of water coadministered with the drug did not affect the bioavailability. The bioavailabilities of slow-dissolving products at pH 3-7.2 under the weakly destructive conditions of the paddle and rotating basket methods were relatively higher in dogs than in humans, which suggested a stronger disintegration force in dogs. Gastric fluid pH seemed to affect the in vivo dissolution of TDS itself. The in vivo parameters in dogs correlated significantly with the dissolution rate, disintegration time and in vivo parameters in high gastric acidity humans, with the exception of one product.View full abstractDownload PDF (841K) -
TSUTOMU KONNO, KOJI KINUNO, KATSUO KATAOKA1986 Volume 34 Issue 1 Pages 301-307
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIt was found that some organic crystalline medicinals such as aspirin and phenacetin, when mixed with an adsorbent, gradually become amorphous during storage at room temperature (25°C). Concomitantly, they show different dissolution patterns and decreased chemical stability. The following observations suggest that this phenomenon takes place via the gaseous phase, induced by the vapor pressure of the medicinal themselves. (1) Subliming crystals such as naphthalene become amorphous immediately in mixtures with adsorbents. (2) The rate of change of medicinals to the amorphous state is accelerated under reduced pressure in these systems. (3) The rate of change of the crystals to the amorphous state increases with their vapor pressure. The technique of treating crystalline medicinals at reduced pressure with an adsorbent may be a useful method of obtaining medicinals in the amorphous state without employing either solvents or excessive thermal or mechanical energy.View full abstractDownload PDF (804K) -
TERUTAKA TAKAHASHI, MASAAKI MORI, YUKO UEZONO, HIROKAZU MAKITA, YUTAKA ...1986 Volume 34 Issue 1 Pages 308-314
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe influence of pharmaceutical properties on the gastric lesions induced by AD-1590 (AD), a non-steroidal anti-inflammatory drug, was investigated in rats.AD, indomethacin (IM) and aspirin (ASA) were orally administered in powder or suspension form to fasted rats. It was found that the gastric ulcerogenic activity of the powder was stronger than that of the suspension in all cases. Thus, the gastric ulcerogenic activity was influenced by the dosage form.Solid preparations of AD having various pharmaceutical properties were orally administered to fasted rats, and it was found that the gastric ulceration caused by AD was associated with the residence time of preparations in the stomach rather than the maximum plasma concentration (Cmax) or extent of bioavailiability (area under the plasma concentration-time curve). Preparations having a long residence time caused gastric ulcers. The gastric ulceration caused by AD might be eliminated by improvement of dissolution and disintegration properties of the drug preparation and by suitable control of gastric emptying. Thus, it appears to be possible to evaluate the influence of pharmaceutical properties on gastric lesions induced by non-steroidal anti-inflammatory drugs (NSAIDs) by using small laboratory animals such as rats.View full abstractDownload PDF (778K) -
YOSHINOBU NAKAI, KEIJI YAMAMOTO, KATSUHIDE TERADA, YASUHIKO UENO1986 Volume 34 Issue 1 Pages 315-319
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSX-Ray analysis, differential thermal analysis (DTA) and infrared (IR) spectroscopy have been used to investigate the influence of the degree of polymerization of oligosaccharides on the dispersion state and the interaction of drugs (aspirin and methylparaben) during grinding with oligosaccharides. When a drug was ground with maltoheptaose or maltopentaose, the crystalline peaks of the drug in the powder X-ray diffraction pattern and the heat of fusion of the drug on DTA disappeared, and some IR spectral changes were observed. In the case of the ground mixture with maltotriose, an amorphous state of the drug was observed from the powder X-ray diffraction and DTA results, but there was no change in the IR spectrum. In the case of the ground mixture with maltose, the crystallinity of the drug was scarcely altered by the grinding.These results indicate that in the ground mixtures with maltopentaose and maltoheptaose, drug molecules were dispersed monomolecularly in the hydrogen-bonded networks of oligosaccharides. On the other hand, in the maltotriose system, although the drug was in an amorphous state, the drug was not in a molecular dispersion due to the low degree of polymerization of maltotriose.View full abstractDownload PDF (546K) -
TOMONARI KUWAYAMA, YUKIHISA KURONO, TSUYUKO MURAMATSU, TAMOTSU YASHIRO ...1986 Volume 34 Issue 1 Pages 320-326
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe hydrolysis of flutazolam and haloxazolam was investigated kinetically. The cleavage reaction of the diazepinone nucleus of flutazolam was reversible, and the ring-cleaved form was in equilibrium with the ring-closed form in aqueous solution. On the other hand, the cleavage reaction of haloxazolam was irreversible. It was concluded that the 2-hydroxyethyl substituent attached to the amide nitrogen atom of flutazolam is responsible for the reversible character of the hydrolytic cleavage of the diazepinone nucleus. The hydrolysis mechanism was elucidated on the basis of the pH-rate profile. To compare the effects of substituents on the hydrolysis, the rate constants of oxazolam and cloxazolam in acidic solution were also determined.View full abstractDownload PDF (723K) -
YASUYUKI TAKAHASHI, NAOKI NAMBU, TSUNEJI NAGAI1986 Volume 34 Issue 1 Pages 327-332
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe coprecipitate of thioridazine hydrochloride, a cationic drug used as a model of watersoluble drug, with pectin was studied to determine the drug dissolution properties in purified water and in hydrochloric acid (pH 1) by means of the modified JP dissolution mehtod.The dissolution pattern of the drug from the coprecipitate in water was shown to fit best with the equation reported by Higuchi, based on the porous penetration hypothesis. The apparent dissolution rate of thioridazine from the coprecipitate in water derived from Higuchi's equation was as follows : coprecipitate<physical mixture with pectin<physical mixture with lactose. A similar result was obtained for these preparations in hydrochloric acid (pH 1). The results suggest that the coprecipitates of cationic water-soluble drugs with pectin may be applicable to sustained-release preparations.View full abstractDownload PDF (592K) -
YASUO MATUSHITA, MASAAKI TAKAHASHI, IKUO MORIGUCHI1986 Volume 34 Issue 1 Pages 333-339
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe quantum yield and binding to bovine serum albumin (BSA) were investigated with various fluorescent 7-alkylamino (bearing 2-12 carbon atoms), 7-benzylamino, and 7-p-methoxybenzyl-amino derivatives of 4-nitrobenzoxadiazole (NBD). Among them, alkylamino derivatives gave high quantum yield in both ethanol and BSA solution, and greater affinity to BSA was found with those having a longer alkyl chain. In particular, those with C8-C12 alkyl chains may be useful in research on hydrophobic regions as fluorescent probes. In the binding of these probes to BSA, the logarithm of the primary association constant increased linearly with increase in the length of the side chain; a hydrophobic cleft similar to that on the human serum albumin molecule was suggested to exist also on the BSA molecule. In the investigation of the binding displacement of 7-amino-NBD derivatives based on Sudlow's classification, almost no displacement was observed with site II drugs, ibuprofen and flufenamic acid. However, diazepam (a site II drug) showed different behavior from other site II drugs. It was particularly interesting that the difference of the displacing behavior between diazepam and other site II drugs increases with increase of the side chain length of the alkylamino-NBD probes.View full abstractDownload PDF (686K) -
MASANORI OKAMOTO, KEIZO YOSHIDA, ITSUO UCHIDA, MOTOAKI NISHIKAWA, MASA ...1986 Volume 34 Issue 1 Pages 340-344
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA platelet activating factor (PAF) antagonist, designated as FR-49175, was isolated from fermentation products of Penicillium terlikowskii and identified as bisdethiobis(methylthio)-gliotoxin (1). The IC50 value of this compound for PAF-induced rabbit platelet aggregation was 8.4 μM.Some derivatives of bisdethiobis(methylthio)gliotoxin (1) were synthesized and their inhibitory activities of PAF-induced platelet aggregation were examined. Among these compounds, 5a, 6-anhydrobisdethio-3, 10a-bis(methylthio)gliotoxin (8) showed the most potent PAF inhibitory activity (IC50; 4.4 μM).View full abstractDownload PDF (635K) -
MASANORI OKAMOTO, KEIZO YOSHIDA, ITSUO UCHIDA, MASANOBU KOHSAKA, HATSU ...1986 Volume 34 Issue 1 Pages 345-348
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSPlatelet activating factor (PAF) antagonistic action of FR-49175 was studied using in vivo models designated as PAF-induced bronchconstriction, hypotension and vascular permeability increase. This compound (0.1 mg/kg, i.v.) significantly inhibited PAF-induced bronchoconstriction in guinea-pigs. However, it did not prevent PAF-induced hypotension in rats or vascular permeability increase in mice. Furthermore, the effect of this compound against a systemic anaphylaxis model in guinea-pigs was examined, but it did not show any inhibition of antigen-induced mortality at the dose of 10 mg/kg, i.v.View full abstractDownload PDF (528K) -
EIICHI SAKURAI, YOSHIKO KIN, GEN FUKUSE, NOBORU HIKICHI, HIROSHI NIWA1986 Volume 34 Issue 1 Pages 349-359
Published: January 25, 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe effects of various cathartics (magnesium sulfate, mannitol, dioctyl sodium sulfosuccinate (DSS), castor oil and pilocarpine) and deoxycholic acid (DCA) on the disposition of endogenous bile acids in the bile, portal blood and feces of rats were investigated. The biliary bile acids of free type increased significantly after the oral administration of cathartics except for DSS. The amounts of glyco- and tauro-conjugated bile acids showed different patterns after the oral administration of various cathartics. However, the proportion of DCA significantly increased in the case of diarrhea induced by cathartics, and the proportion of cholic acid (CA) conversely decreased compared with the control. Thus, it was suggested that unconjugated bile acids eliminated into the intestinal lumen and DCA formed from CA participate in the occurrence of diarrhea after oral administration of various cathartics. Moreover, the ratio of glycine- to taurine-conjugated bile acid of rat bile increased when diarrhea was induced by various cathartics. Thus result suggested that the reabsorption of tauro-conjugated bile acids is decreased, or that the reabsorption of glyco-conjugated bile is increased in diarrhea.On the other hand, DCA caused diarrhea in rats. The occurrence of diarrhea was concentrated within 20 to 24 h after the oral administration of DCA. Since biliary unconjugated and glyco-conjugated bile acids were increased at 24 h after DCA treatment, whereas glyco-conjugated bile acids were decreased in the portal blood, it is conceivable that deconjugation is accelerated by changes in the activity of intestinal bacteria and in the liver after DCA treatment. Active transport of tauro-conjugated bile acids from the end of the ileum may have been impaired, because the absorption of tauro-conjugated bile acids was inhibited from 1 h after the administration of DCA.View full abstractDownload PDF (1000K) -
KEITO BOKI, SEIKI TANADA, RYOJI YAMASAKI, NOBUHIRO OHTANI, HIROYUKI TE ...1986 Volume 34 Issue 1 Pages 360-365
Published: 1986
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn order to ensure the effective adsorptive removal of orthophosphate ion from solution, the adsorption equilibrium and adsorption rate of orthophosphate ion on activated carbon were measured at 30°C. The Freundlich equation was applicable to the adsorption isotherms, but an infection was observed in the Freundlich plots of the isotherms. It was concluded that the inflection is a consequence of the pore size distribution of the porous activated carbon. The amounts of orthophosphate ion adsorbed at low concentration and at high concentration seemed to be affected by pH and pore volume, respectively. The adsorption rate of orthophosphate ion into the pores of activated carbon was investigated on the basis of the intraparticle diffusivity (Di') determined by a batch method. The value of Di' changed with the adsorption ratio (F). In the range of constant Di', regardless of F, intraparticle diffusivity was affected by the surface diffusivity rather than the pore diffusivity. The transitional pore volume of activated carbon contributed predominantly to the intraparticle diffusivity of orthophosphate ion.View full abstractDownload PDF (658K)