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Volume 33, Issue 7
Displaying 1-50 of 73 articles from this issue
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SEIJI KATAYAMA, HIIZU IWAMURA, ISHIMATSU KATO1985 Volume 33 Issue 7 Pages 2635-2640
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe pH and concentration dependencies of proton and oxygen exchanges in water-solvent systems have been examined by oxygen-17 nuclear magnetic resonance (17O-NMR) spectroscopy. A pH shift in a water-acetone system results in a coalescence of the 17O water signal and an alteration in the intensities of the signals of water and acetone. The signal coalescence arises from proton exchange between water molecules and the signal alteration from oxygen exchange between water and solvent. On the other hand, dilution with solvent results in various patterns of 17O water signals from singlet to triplet. Each water-solvent sample under diluted conditions gives a specific shape which reflects the intrinsic nature of the solvent. In this case, the proton exchange can be discussed by assuming a simplified reaction mechanism. [chemical formula] It is concluded that the Fi factor, which refers to a contribution arising from water-solvent interaction, can be taken as a good measure of proton exchange in water-solvent systems and is available for the characterization of solvents soluble in water.View full abstractDownload PDF (554K) -
YESOOK KIM, KATSUNOSUKE MACHIDA, TOORU TAGA, KENJI OSAKI1985 Volume 33 Issue 7 Pages 2641-2647
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe crystal structure of aspirin has been redetermined by X-ray diffraction analysis at room temperature. The lattice energy, the eleastic constants and the structure parameters corresponding to the equilibrium of a model potential of aspirin crystal have been calculated by taking account of the non-rigidity of the molecule and applying the condition of vanishing stress. The model potential consists of the exp-6 type dispersion and exchange repulsion terms, the Lippincott type hydrogen bond stretching terms and the electrostatic interaction terms between fixed atomic charges. The atomic coordinates of the calculated structure agree well with those determined crystallographically.View full abstractDownload PDF (686K) -
JUZIRO NISHIJO, NORIKO MORITA, SHOZO ASADA, HIROKO NAKAE, EMIKO IWAMOT ...1985 Volume 33 Issue 7 Pages 2648-2653
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe interaction of theophylline with bovine serum albumin (BSA) was studied at pH 6.85, using the equilibrium dialysis method. The investigation was carried out at three different temperatures, 15, 25, and 37°C. The data were analyzed by assuming two types of independent binding sites, and the binding parameters and thermodynamic parameters were determined to be as follows ; n^^-1=0.61, ΔH1=-9.72 kcal/mol, ΔS1=-19.0 (e.u.) (ΔG1=-3.93 kcal/mol at 25°C), n^^-2=1.19, ΔH2=-2.86 kcal/mol, ΔS2=1.6 (e.u.) (ΔG2=-3.34 kcal/mol at 25°C). It was also found that benzoic acid binds to BSA in competition with theophylline. The interaction of benzoic acid with BSA was studied in the same way as that of theophylline and the binding parameters and thermodynamic parameters were determined to be as follows ; n^^-1=0.91, ΔH1=-8.81 kcal/mol, ΔS1=-7.5 (e.u.) (ΔG1=-6.59 kcal/mol at 25°C), n^^-2=2.94, ΔH2=-3.32 kcal/mol, ΔS2=4.7 (e.u.) (ΔG2=-4.71 kcal/mol at 25°C). The general features of the thermodynamic parameters for both theophylline and benzoic acid were similar to those of salicylic acid. Quenching of the fluorescence of tryptophan residues on BSA in the presence of theophylline or benzoic acid was observed. On the basis of all the experimental results, it is considered that theophylline and benzoic acid bind primarily to tryptophan residue on BSA by stacking due to van der Waals forces and secondarily bind to other amino acid residues on BSA through ionic and hydrophobic interactions.View full abstractDownload PDF (629K) -
MASAYUKI NAKAGAKI, SHOKO YOKOYAMA1985 Volume 33 Issue 7 Pages 2654-2662
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe distribution of acetylcholine chloride (Ach) between the aqueous and micellar phases has been measured by means of ultrafiltration and the binding parameters have been estimated. The results indicate that Ach enters not only anionic micelles of sodium dodecyl sulfate (SDS), but also cationic micelles of dodecyltrimethylammonium chloride (DTAC). Furthermore, in the cases of ionic micelles and mixed micelles composed of ionic and nonionic, (heptaethylene glycol dodecyl ether (HED)), surfactants, it has been found that Ach molecules are bound to one locus within the surfactant micelles. The Ach molecule has higher affinity but lower saturated adsorption amount for DTAC micelles than SDS micelles, indicating that Ach molecules are probably situated at the surface of the SDS micelles, but penetrate more deeply and bind more tightly to DTAC micelles. For nonionic micelles, the bound Ach concentration (percent) was very small, but for mixed micelles, the percentage increased with mole fraction of ionic surfactants. Furthermore, in the system of negatively charged mixed micelles and Ach, the bound Ach concentration (percent) was found to depend on the surface potential of the micelles, and the dependence was explained well by the Gouy-Chapman theory.View full abstractDownload PDF (826K) -
TERUHISA FUJIMAKI, HIROMASA NAGASE, RYOJI YAMAGUCHI, KENICHI KAWAI, HI ...1985 Volume 33 Issue 7 Pages 2663-2670
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2-Methyl-1, 3 (2H, 4H)-isoquinolinedione (I) reacted with methylglyoxal to form 1, 1-bis (2-methyl-1, 3-dioxo-1, 2, 3, 4-tetrahydroisoquinolin-4-yl) acetone (IV) in 58% yield. The Michael reaction of 2-methyl-4-phenacylidene-1, 3 (2H, 4H)-isoquinolinedione (II) with malononitrile gave 1H-pyrano [2, 3-c] isoquinoline (VI) and furo [2', 3' : 2, 3] furo [5, 4-c] isoquinoline (VII) derivatives in a ratio of 2 : 3. In the reaction of IV with malononitrile, retrograde Michael reaction occurred and resulted in the formation of 1, 1H-pyrano [2, 3-c] isoquinoline (IX) and 4-3'-furyl-1, 3 (2H, 4H)-isoquinolinedione (X) derivatives. X-Ray structure analyses of VII and IX were performed.View full abstractDownload PDF (693K) -
NOBUYA KATAGIRI, TORU HANEDA, RYUJI NIWA, TETSUZO KATO1985 Volume 33 Issue 7 Pages 2671-2677
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSReaction of 2, 3, 5-tri-O-benzyl-D-ribofuranose (4) with carboalkoxychloromethylenetriphenyl-phosphoranes (5a, b) gave an E, Z mixture of the corresponding alkyl 4, 5, 7-tri-O-benzyl-2-chloro-2, 3-dideoxy-D-ribo-hept-2-enonates (6a, b). Cyclization of 6a, b with triethylamine afforded exclusively the β-C-glycosides 7a, b which were diastereomeric at the carbon bearing chlorine. Hydrolysis of 7a, b with 5% aq. sodium hydroxide in dioxane gave the carboxylic acid 8. Treatment of 8 with thionyl chloride (or trifluoroacetic anhydride) in the presence of triethylamine, followed by reaction with the 2-arylideneaminopyridine 2a or ethyl N-(2-pyridyl) formimidates (2b, c) gave the corresponding fully protected pyrido [1, 2-a] pyrimidine C-nucleosides (15a-c), which were deprotected with boron trichloride to give the C-nucleosides (17b, c).View full abstractDownload PDF (854K) -
YOSHIKO MIYAMOTO1985 Volume 33 Issue 7 Pages 2678-2687
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSCondensation of diaminomethylenehydrazones with ethoxymethylenemalononitrile (2) gave 2, 3-dihydro [1, 2, 4] triazolo [1, 5-c] pyrimidines in moderate to high yields. Of the variously substituted diaminomethylenehydrazones, amino (monosubstituted amino) methylene ones were most reactive in this condensation, regardless of the nature of the 4-substitutent. The reaction was found to be initiated at N-3 by attack on the ethoxymethine carbon of 2, followed by an electrocyclic reaction to form the bicyclic pyrimidine. The 2, 3-dihydro compounds were oxidized with iron (III) chloride in aqueous acetic acid or iodine in ethyl alcohol to give the corresponding [1, 2, 4] triazolo [1, 5-c] pyrimidines.View full abstractDownload PDF (823K) -
KOICHI KOJIMA, SHIGEO AMEMIYA, KAZUO KOYAMA, KIYOSHI SAKAI1985 Volume 33 Issue 7 Pages 2688-2696
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS(+)-9 (O)-Methanoprostacyclin (1a) and (-)-ent-9 (O)-methanoprostacyclin (1c) were synthesized from the bicyclic esters, methyl (+)-(1S, 2R, 3R, 5R)-3-hydroxy-7, 7-ethylenedioxybicyclo-[3.3.0] octane-2-carboxylate (2a) and methyl (-)-(1R, 2S, 3S, 5S)-3-hydroxy-7, 7-ethylenedioxybicyclo [3.3.0] octane-2-carboxylate (2b), respectively, which were obtained by optical resolution of the racemic acid (3), followed by esterification. The absolute configurations of 2a and 2b were determined by the chemical correlation method. (+)-9 (O)-Methanoprostacyclin (1a) was found to be as active as prostaglandin E1, and (-)-ent-9 (O)-methanoprostacyclin (1c) was considerably less active than 1a, in inhibiting platelet aggregation.View full abstractDownload PDF (1076K) -
TOZO FUJII, YUKIMI TAKAI, MASASHI OHBA, HIROSHI KOGEN, MICHINORI OKI1985 Volume 33 Issue 7 Pages 2697-2704
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new method for differentiating the lactam CO infrared (IR) absorption from the C=C absorption in the six-membered, α, β-unsaturated lactam system (type 2) has been developed by utilizing association of dichloroacetic acid or a similar carboxylic acid with the lactam CO, which decreases the frequency of the lactam CO absorption by 20-40 cm-1. On the basis of such an association shift as well as the results obtained from solvent shift experiments with the lactams 5, 6, 15, and 17-19, the lactam CO and the conjugated C=C absorptions observed for each of the α, β-unsaturated lactams 14-19 in the 1590-1670 cm-1 region were differentiated from each other. As a result, it has now become clear that in six-membered lactams the carbonyl frequency is slightly (10-20 cm-1) lowered by conjugation with a double bond, in line with the usual lowering. This is the opposite of what has been proposed in the literature. In addition, the deuterated α, β-unsaturated lactam 24 was prepared from the exocyclic methylene lactam 23 by treatment with NaOD in a mixture of D2O and EtOD. This deuterium labeling was found to decrease the frequency of the 1666 cm-1 absorption, assigned to the C=C stretching vibration, by 17 cm-1, supporting the correctness of the above differentiation.View full abstractDownload PDF (775K) -
HIROSHI HARA, OSAMU HOSHINO, BUNSUKE UMEZAWA1985 Volume 33 Issue 7 Pages 2705-2711
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTreatment of the N-benzyl p-quinol acetates 2a and 2b with trifluoroacetic acid gave dibenzo [c, f]-1-azabicyclo [3.3.1] nonanes (3a and 3b) in good yields. The homologs 3c, 3d, and 3e were similarly prepared from the N-phenethyl p-quinol acetates 2c, 2d, and 2e, respectively. On the other hand, the o-quinol acetate (17), obtained from the tetrahydroisoquinolin-6-ol (9) by lead tetraacetate oxidation, was rearranged to the 4-acetoxy derivative (18). Acid treatment of 18 induced cyclization to construct the same skeleton as that of 3a.View full abstractDownload PDF (592K) -
FUMIKO ABE, TATSUO YAMAUCHI1985 Volume 33 Issue 7 Pages 2712-2720
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSEsters of p-O-glucosyl-and p-O-primverosylnervogenic acid with some carbohydrates (including dambonitol, glucose, and sucrose) were isolated from the seeds, unripened fruits, and caules of Anodendron affine DRUCE. The locations of the nervogenic acid moiety on dambonitol and sucrose were determined on the basis of spectral and chemical evidence.View full abstractDownload PDF (858K) -
MASAICHIRO MASUI, KOICHI NOSE, SATOMI TERAUCHI, EIKO YAMAKAWA, JISOOK ...1985 Volume 33 Issue 7 Pages 2721-2730
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSElectrochemical oxidation of N-nitrosamines (1) derived from symmetrical dialkylamines was investigated in acetonitrile in the presence of dissolved oxygen. On cyclic voltammetry at ambient temperature, 1 showed two or three irreversible anodic peaks, depending upon the structure. Macroscale electrolysis, either controlled potential or constant current, of 1 which showed three voltammetric peaks gave the corresponding nitramine (2) and N-alkyl-N-(2-oxoalkyl) nitrosamine (3) as the main products. In the case of 1 which showed two voltammetric peaks, however, the sidechain oxidized nitrosamine 3 was not obtained. It is suggested that the oxygen atom incorporated in the products 2 and 3 originated from dioxygen dissolved in the medium, and that the numbers of electrons required for the formation of 2 and 3 are one and two, respectively. A possible reaction sequence, which involves the reactions of the radical cation (4) derived from 1 and a radical formed by intramolecular rearrangement of 4 with dioxygen, is proposed.View full abstractDownload PDF (980K) -
TAKUO CHIBA, TAKUMI TAKAHASHI1985 Volume 33 Issue 7 Pages 2731-2734
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe reaction of 4-ethoxymethylene-2-phenyl-5-oxazolone (1) with 3-amino-2-butenoates (2a-2c) gave 1-substituted 3-benzamido-5-ethoxycarbonyl-6-methyl-2-(1H)-pyridones (4a-4c) in 56-77% yields. Similarly, compound 1 reacted with 3-amino-2-butenamides (3a and 3b) to yield 1-substituted 3-benzamido-5-carbamoyl-6-methyl-2 (1H)-pyridones (7a and 7b). In the reaction of compound 1 with arylaminobutenamides (3c and 3d), 5-carbamoyl-2 (1H)-pyridones (7c and 7d) and 5-cyano-2 (1H)-pyridones (8c and 8d) were obtained.View full abstractDownload PDF (480K) -
MICHIAKI YONEDA, MASAMI SHIRATSUCHI, MITSUO YOSHIMURA, YASUSHI OHKAWA, ...1985 Volume 33 Issue 7 Pages 2735-2742
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIt was confirmed that the title compound, a new antihypertensive drug, consists of four optical isomers : two diastereomers and their enantiomers. Separation of the diastereomers was effected by recrystallization. Optical resolution of the enantiomers was carried out by repeated recrystallization of their diastereomeric salts with (+)-or (-)-2-[1-(p-chlorobenzoyl)-5-methoxy-2-methylindol-3-yl] acetoxy-2-phenylacetic acid or by high performance liquid chromatography of the L-menthoxyacetyl derivatives. The absolute configurations of the separated isomers were determined on the basis of the circular dichroism spectra and proton nuclear magnetic resonance spectra.View full abstractDownload PDF (781K) -
CHUNSHENG CHIEN, TOMOMI KAWASAKI, MASANORI SAKAMOTO, YASUMITSU TAMURA, ...1985 Volume 33 Issue 7 Pages 2743-2749
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe epoxidation of cis-2-butene-1, 4-diones 4 with (aqua) (hexamethylphosphoramide) oxodiperoxomolybdenum (VI), MoO5·H2O·HMPA, occurred stereospecifically to give the cisepoxides 5, whose stereochemistry was assigned on the basis of chemical evidence and a comparison of their spectral data with those of the coresponding trans-epoxides 6, which were prepared by the epoxidation of the trans-olefins 3 with alkaline hydrogen peroxide.View full abstractDownload PDF (779K) -
KOICHI KOJIMA, SHIGEO AMEMIYA, HIROSHI SUEMUNE, KIYOSHI SAKAI1985 Volume 33 Issue 7 Pages 2750-2761
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA general method for the stereospecific synthesis of 2, 3-trans-3, 4-cis-trisubstituted cyclopentanones (9) is described. This synthetic method has the advantage that three functional groups can be stereospecifically introduced on a five-membered ring by the catalytic hydrogenation of 2, 3, 4-trisubstituted cyclopentenones. Furthermore, 9 could be stereospecifically converted to 1, 2-trans-2, 3-trans-3, 4-cis-trisubstituted cyclopentanols (20) and 3, 4-cis-disubstituted cyclopentanones (11) by a simple procedure. These synthetic methods may be useful for the synthesis of natural products containing a five-membered ring.View full abstractDownload PDF (975K) -
YOSHIYASU TERAO, HIROMI KOTAKI, NOBUYUKI IMAI, KAZUO ACHIWA1985 Volume 33 Issue 7 Pages 2762-2766
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe 1, 3-dipolar cycloaddition of an intermediary iminium ylide formed from N-benzyl-N-(methoxymethyl) trimethylsilylmethylamine to conjugated olefinic and acetylenic dipolarophiles in the presence of a catalytic amount of trifluoroacetic acid has been found to give 3-or 3, 4-substituted pyrrolidines and 2, 5-dihydropyrroles.View full abstractDownload PDF (457K) -
KAZUTAKE SHIMADA, JAISEUP RO, KAZUO OHISHI, TOSHIO NAMBARA1985 Volume 33 Issue 7 Pages 2767-2771
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new bufotoxin having glutaric acid as a dicarboxylic acid moiety was found in the Korean toad, Bufo bufo gargarizans CANTOR. This new bufotoxin was separated from the dried toad by usual chromatographic methods including reversed phase high-performance liquid chromatography, and its structure was elucidated to be cinobufagin 3-glutaroyl-L-arginine ester by degradative and synthetic means. In addition, seven known bufogenins and eight known bufotoxins were isolated and characterized.View full abstractDownload PDF (588K) -
MASAKO TAKANI, KOTARO TAKAHASHI1985 Volume 33 Issue 7 Pages 2772-2777
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe structures of photolysis products of diacetylusnic acid, usnic acid, isoxazolo [4, 5-b] usnic acid, and isoxazolo [4, 5-a] usnic acid in the presence of nucleophiles were studied and the mechanisms of the photolyses are discussed.View full abstractDownload PDF (638K) -
JUNICHI KUNITOMO, SAYURI KAEDE, MIYOKO SATOH1985 Volume 33 Issue 7 Pages 2778-2782
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSTwo structurally unidentified alkaloids (tentatively named bases III and IV), isolated from Menispermum dauricum DC. (Menispermaceae), were found to be dauriporphine (1), a known oxoisoaporphine-type alkaloid, and 2, 3-dihydromenisporphine (3), a new alkaloid of the same type, respectively. The structure of dauriporphine was confirmed by synthesis of 4, 5, 6, 9-tetramethoxy-7H-dibenzo [de, h] quinolin-7-one (1).View full abstractDownload PDF (638K) -
NAOKO MORISAKI, JUN FURUKAWA, HISAYOSHI KOBAYASHI, SHIGEO IWASAKI, AKI ...1985 Volume 33 Issue 7 Pages 2783-2791
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS8-Hydroxy-6-protoilludene (9), a probable biosynthetic intermediate of humulene-derived sesquiterpenes, was synthesized. A synthetic intermediate, the 2, 9-cis-2, 3-anti enone 15, was found to be unstable under basic conditions and was readily isomerized to the trans-anti isomer 23.View full abstractDownload PDF (863K) -
NAOKO MORISAKI, JUN FURUKAWA, HISAYOSHI KOBAYASHI, SHIGEO IWASAKI, AKI ...1985 Volume 33 Issue 7 Pages 2792-2797
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSBoth 9-epi-6-protoilluden-8-one (5) and 6-protoilluden-8-one (4) underwent cyclobutylcyclopropylcarbinyl cation rearrangement on treatment with CF3COOH (25%)-CHCl3, to give 2, 9-cis-2, 3-syn 6-protoilluden-8-one (6). In order to elucidate the relative thermodynamic stabilities of these stereoisomeric enones (4-7), molecular mechanical calculations were carried out. The result showed that the cis-syn enone 6 is the most stable one. This is in good agreement with the experimental results.View full abstractDownload PDF (547K) -
JEAN-CHARLES LANCELOT, SYLVAIN RAULT, DANIEL LADUREE, MAX ROBBA1985 Volume 33 Issue 7 Pages 2798-2802
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSPyrido [3, 2-e] pyrrolo [1, 2-a] pyrazines are prepared by intramolecular cyclization of (pyrrolyl-1)-2 pyridine derivatives. Proton magnetic resonance (1H-NMR) are studied.View full abstractDownload PDF (584K) -
HARUO TANAKA, IKUO MORIGUCHI, SHUICHI HIRONO, SATOSHI OMURA1985 Volume 33 Issue 7 Pages 2803-2808
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSQuantitative structure-activity relationships analyses of O-acylleucomycins for antimicrobial and ribosome-binding activities were carried out based on partition coefficient values. The analyses indicate that the antimicrobial activity against gram-positive bacteria (Bacillus subtilis, Staphylococcus aureus and Micrococcus luteus) and the ribosome-binding activity are parabolically related to the hydrophobic character, and that the local hydrophobicity of the 3"-O-acyl group which is attached to the tertiary hydroxyl function is especially significant for the antimicrobial action. The correlation of antibacterial activity against gram-positive bacteria with ribosome-binding activity is also significant, but that in the case of gram-negative Escherichia coli is very poor. This discrepancy is considered to arise because the antimicrobial activity depends strongly on the ability of the drugs to permeate through the outer membranes (gram-positive bacteria do not have such membranes).View full abstractDownload PDF (576K) -
Synthesis and Inhibitory Effect on Platelet Aggregation of 2-Phenyl-1 (2H)-phthalazinone DerivativesAKIKO SUGIMOTO, KEIKO SAKAMOTO, YOHKO FUJINO, YOSHIMI TAKASHIMA, MASAY ...1985 Volume 33 Issue 7 Pages 2809-2820
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2-Phenyl-1 (2H)-phthalazinone derivatives (4) were synthesized by the reactions of corresponding o-phthalaldehydic acids (5) with phenylhydrazine derivatives. The preparation of 5 was carried out by decarboxylation of keto-carboxylic acids (6) or hydroxylation of phthalides (8) via their bromo derivatives (9). The derivatives (4) were tested for inhibitory activity on platelet aggregation. None of them showed any appreciable effect on platelet aggregation induced by adenosine diphosphate. Several compounds (4l, 4m, 16a, and 16c), however, effectively inhibited platelet aggregation induced by arachidonic acid.View full abstractDownload PDF (1215K) -
SETSUKO OIKAWA, MINORU TSUDA, KIKUTAROU ENDOU, HIDEKO ABE, MAYUMI MATS ...1985 Volume 33 Issue 7 Pages 2821-2831
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA structure-activity relationship between antibacterial activity and the energy of the lowest unoccupied molecular orbital (LUMO) of phenolic and aromatic nitro compounds was derived based on results obtained with eight strains of Gram-positive and Gram-negative bacteria. The reliability of the correlation was confirmed by measuring the minimum inhibitory concentration at various pH values of the medium ; it was found that the undissociated molecular species having a low lying LUMO is essential for strong antibacterial activity. Based on the above results, 2, 4, 6-trinitroanisole was examined, and it proved to have a remarkably strong antibacterial activity (200 times stronger than that of 2, 4, 6-trinitrophenol).View full abstractDownload PDF (912K) -
TOMONORI HOSHIKO, SHOICHIRO OZAKI, YUTAKA WATANABE, TOMIO OGASAWARA, S ...1985 Volume 33 Issue 7 Pages 2832-2837
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA series of 5-fluorouracil derivatives having (alkylthio) carbonyl groups at the 1-, 3-, and 1, 3-positions was synthesized and tested for antitumor activity against L-1210 leukemia in mice. Among them, 1-(octylthio) carbonyl-5-fluorouracil showed promising activity ; it gave a greater increase in life span than 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(2-tetrahydrofuryl)-5-fluorouracil (Tegafur), which are both in clinical use.View full abstractDownload PDF (568K) -
FUMIYOSHI ISHIKAWA, MASAYUKI KITAGAWA, YOSHINARI SATOH, JUNJI SAEGUSA, ...1985 Volume 33 Issue 7 Pages 2838-2848
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA series of (substituted phenyl)-2, 3, 5, 6-tetrahydro-1H-imidazo [1, 2-a] imidazoles (10) and their 2- or 3-oxo derivatives (20 and 21) were unambiguously prepared. These compounds were evaluated for antihypertensive and diuretic activities. Antihypertensive activity in spontaneously hypertensive rats (SHR) was observed in the series of compounds 10, whereas compounds 20 and 21 did not possess the activity. Diuretic effects in SHR and normotensive rats were observed in both the series of 10 and the 2- or 3-oxo derivatives (20 and 21). The relationship between the activities and the substituents on the phenyl ring is discussed.View full abstractDownload PDF (988K) -
HIROKO KIMATA, NAMI SUMIDA, NORIKO MATSUFUJI, TOSHINOBU MORITA, KEIKO ...1985 Volume 33 Issue 7 Pages 2849-2853
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe possible presence of a solubilizing substance for saikosaponin-a, which is sparingly soluble in water, was investigated in Ginseng which is sometimes co-prescribed in decoctions of oriental traditional medicines. It was found that the water solubility of saikosaponin-a was not influenced in the presence of dammarane saponins but was remarkably increased in the presence of chikusetsusaponin V (=ginsenoside-Ro), a bisdesmoside of oleanolic acid. The solubilizing activity of chikusetsusaponin V was estimated by determining the surface tension of aqueous solutions. No influence of chikusetsusaponin V on the hemolytic activity of saikosaponin-a was observed.View full abstractDownload PDF (539K) -
YOSHITAKA OHISHI, KIYOSHI KURIYAMA, YOSHIO DOI, TERUO NAKANISHI1985 Volume 33 Issue 7 Pages 2854-2861
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe antibacterial activities of a series of 2-nitrobenzo [b] furan derivatives against St. aureus, B. subtilis, E. coli, Sal. typhimurium, Sal. enteritidis, Sh. flexneri, Pr. vulgaris or Ps. aeruginosa were determined in vitro. Most of the compounds showed considerable activities against the bacteria except Pr. vulgaris and Ps. aeruginosa and one of them was about 30 times as active as nitrofurantoin against St. aureus. Mono- and dimethoxy derivatives (2a, 3a, 4a, 5f) were the most active. The polarographic half-wave potentials (E1/2) of the 2-nitrobenzo [b] furans at pH 7 were in a narrow range of -0.450±0.04 V, whereas the E1/2 values of regioisomeric nitrobenzo [b] furans were more negative (-0.560--0.726 V). In the case of 2-nitrobenzo [b] furans, substituent (s) on the benzene ring had little influence on the reduction potential of the 2-nitro group, whereas the antibacterial activity depended markedly on the substituent group (s).View full abstractDownload PDF (794K) -
MUTSUKO OHTA, MASATAKE IWASAKI, KEIKI KOUNO, YO UEDA1985 Volume 33 Issue 7 Pages 2862-2865
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS2-Methyl-1-naphthol was found to develop characteristic color with hexoses and pentoses in concentrated sulfuric acid very sensitively, and was used to elucidate the reaction mechanism of the Molisch reaction. The chemical structures of the reaction product of glucose (I) and that of rhamnose (II) were established to be 2-[(4-hydroxy-3-methyl-naphth-1-yl) methyl]-5-[(3-methyl-4-oxo-naphth-1-ylidene) methyl] furan and 5-[(3-methyl-4-oxo-naphth-1-ylidene) methyl]-2-methylfuran, respectively.View full abstractDownload PDF (506K) -
HIROTERU SAYO, MIKIO HOSOKAWA1985 Volume 33 Issue 7 Pages 2866-2870
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSWe describe a spin immunoassay (SIA) in which the two antiepileptic agents, phenytoin (PHT) and phenobarbital (PB), are determined simultaneously in a single measurement. The method involves labeling the two with 15N-and 14N-nitroxide, respectively, whose electron spin resonance peaks do not overlap each other. With 2μl of serum, the smallest detectable concentration for either drug was 1.25 mg/l. PHT and PB levels in Q-PAK therapeutic drug-monitoring control sera were determined by SIA. The values obtained by SIA were in good agreement with those presented by the manufacturer. Sera from rabbits after administration of PHT and/or PB were analyzed by SIA and high-performance liquid chromatography. There was a good correlation between results obtained by the two methods.View full abstractDownload PDF (587K) -
MIKIO OHNISHI, HIROYUKI SUGIMOTO, HIDENORI YAMADA, TAIJI IMOTO, KIYOSH ...1985 Volume 33 Issue 7 Pages 2871-2876
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThree water-soluble bovine serum albumin derivatives with carboxyl spacer groups have been synthesized as carrier proteins for direct preparation of conjugates between proteins and low molecular haptens with amino groups. N-Glycylaminomethanesulfonic acid, a newly developed solubilizing reagent for proteins, was first introduced into bovine serum albumin through its carboxyl groups. After the methylation of carboxyl groups remaining unreacted in the modified albumin, N-succinylglycine and N-bromoacetyl-β-alanine, both carboxyl spacer reagents, were reacted with the amino or imidazole groups of the modified albumin, respectively, to give two water-soluble albumin derivatives. Another water-soluble albumin derivatives. Another water-soluble albumin derivative was obtained by treating the modified albumin with N-bromoacetyl-β-alanine followed by amidination of the remaining amino groups of the albumin with methylacetimidate. Glycine ethyl ester, selected as a model hapten that has an amino group, was reacted with these albumin derivatives to form conjugates, and 4-15 ester moieties can be incorporated into one molecule of the albumin derivatives without loss of their water-solubility.View full abstractDownload PDF (658K) -
TAKEHIKO NOHMI, MOTOI JR. ISHIDATE, AKIRA HIRATSUKA, TADASHI WATABE1985 Volume 33 Issue 7 Pages 2877-2885
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSBucetin (N-(β-hydroxybutyryl)-p-phenetidine) was found to be mutagenic to Salmonella typhimurium TA100 in the presence of liver 9000g supernatant fractions (S9) prepared from polychlorinated biphenyl (PCB)-treated hamsters and a reduced nicotinamide adenine dinucleotidephosphate (NADPH)-generating system. However, the analgetic was not mutagenic in the presence of NADPH-fortified S9 from PCB-treated rat liver. The mutagenic potency of bucetin was about a quarter of that of the structurally related analgetic, phenacetin. PCB-treated hamster liver microsomes fortified with NADPH activated bucetin to two direct-acting mutagens, N-hydroxyphenetidine and p-nitrosophenetole, through deacylation followed by N-hydroxylation. The nitroso compound arose from N-hydroxyphenetidine via autoxidation. N-(β-Hydroxybutyryl)-p-aminophenol, a major metabolite of bucetin under the conditions used, was not mutagenic to TA 100 either with or without NADPH-fortified S9 from PCB-treated or untreated rats or hamsters. N-Hydroxybucetin, which was about 70 times less mutagenic than N-hydroxyphenacetin in the presence of PCB-treated hamster S9, was not detected as a metabolite of bucetin from the NADPH-fortified reaction mixtures. Although no species difference was observed in p-phenetidine N-hydroxylation, the rate of bucetin deacylation was over 90 times higher in hamsters than in rats. The rate of microsomal deacylation of bucetin was much lower than that of phenacetin or N-butyryl-p-phenetidine. These results suggest that the species difference in bucetin mutagenicity is due to the difference in deacylating activity between rat and hamster liver microsomes, and also that the β-hydroxyl group in the butyryl side chain makes bucetin poorly hydrolyzable in microsomes, resulting in lower mutagenic activity as compared with phenacetin.View full abstractDownload PDF (982K) -
ICHITOMO MIWA, HIROHISA FUJII, JUN OKUDA1985 Volume 33 Issue 7 Pages 2886-2889
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIt was examined whether or not a rate-limiting anomerization step is present in the pathway of glycogen synthesis from glucose, in which phosphoglucomutase is known to act specifically on the α anomer of glucose 6-phosphate. Glycogen synthesis from the α and β anomers of D-[U-14C] glucose in rat hemidiaphragms was measured by aerobic incubation in Krebs-Ringer bicarbonate buffer (pH 7.4) at 37°C for short periods (1 or 3 min) in the presence or absence of insulin (10 mU/ml). There was no statistically significant difference between the rates of glycogen synthesis from the two anomers of glucose under various conditions. These findings suggest that there is no rate-limiting anomerization step in the pathway of glycogen synthesis from glucose in the muscle.View full abstractDownload PDF (526K) -
TAKUO KOSUGE, KUNIRO TSUJI, KOICHI HIRAI, TOSHINORI FUKUYAMA, HARUO NU ...1985 Volume 33 Issue 7 Pages 2890-2895
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new toxin, named prosurugatoxin because it formed surugatoxin on decomposition, was isolated from the toxicated Japanese ivory shell (Babylonia japonica). Prosurugatoxin evoked mydriasis in mice at a minimum effective intraperitoneal dose of 15 ng/g body weight, and inhibited the contractile response of isolated guinea pig ileum induced by 3×10-5g/ml of nicotine at a concentration of 5×10-9g/ml. In this mollusc the prosurugatoxin content was about 5 times that of neosurugatoxin. Prosurugatoxin was deduced on the basis of physical and chemical data to be des-xylopyranosyl-neosurugatoxin.View full abstractDownload PDF (543K) -
NOBORU SUZUKI, TETSUYA NAKAMURA, HIDEYUKI ISHIDA, KIYOSHI HOSONO1985 Volume 33 Issue 7 Pages 2896-2903
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSHeart cells from mouse embryos were cultured in either 5% CO2 and 95% air or 5% CO2 and 95% N2. Single myocardial cells showed frequent irregular beating under both conditions. Using this experimental system, we studied the effect of coenzyme Q10 (CoQ10) on the cellular functions of myocardial cells. Under the hypoxic conditions, CoQ10 decreased the irregular beating frequency without changing the beating rate. CoQ10 increased the cardiac adenosine 3', 5'-cyclic monophosphate (cAMP) level under the normal conditions and tended to decrease cardiac cAMP level under the hypoxic conditions. After incubation of deuterium-labeled CoQ10 (CoQ10-d5), the presence and levels of endogenous CoQ9, CoQ10 and exogenous CoQ10 were determined. Endogenous CoQ9 and CoQ10 were found in the mitochondrial fraction. Exogenous CoQ10 was found in the plasma membrane, cytosol and mitochondrial fractions. These findings confirm the protective effect of CoQ10 in ischemic heart disease. The exogeneous CoQ10 may provide protection against ischemic cellular damage by modulating cell functions.View full abstractDownload PDF (850K) -
YOSHIHIKO INAMORI, MAYURI KUBO, YOSHIAKI KATO, MASAHIDE YASUDA, HIROSH ...1985 Volume 33 Issue 7 Pages 2904-2909
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new compound, 3, 4-O-isopropylidene-3, 3', 4, 5'-tetrahydroxystilbene (I), chemically derived from 3, 3', 4, 5'-tetrahydroxystilbene (II) showed strong antifungal activity, ichthyotoxicity, coronary vasodilator action on the isolated guinea-pig heart and a hypotensive effect on rats. These activities of I were much stronger than those of the original substance (II). As regards antifungal activity, the minimal growth inhibitory concentrations (MIC) of I for Trichophyton mentagrophytes and Fusarium oxysporum f. sp. lycopersici were 6 and 1μg/ml, respectively. As regards ichthyotoxic activity, the median tolerance limit (TLm) at 48 h was 14.0 ppm in Oryzias latipes TEMMINCK et SCHLEGEL. Compound (I) also had strong coronary vasodilator action on guinea-pig heart in vitro ; the ED50 value was 4.5μg/heart. Finally, I showed a strong hypotensive effect on rats (-43.0±5.2mmHg, 10mg/kg i.v.).View full abstractDownload PDF (661K) -
MAYURI KUBO, YOSHIAKI KATO, NAGAYO OTA, TSUNEMATSU TAKEMOTO, KYOSUKE N ...1985 Volume 33 Issue 7 Pages 2910-2915
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe mechanisms of phytogrowth-inhibitory action of racemomycin-D were investigated by means of histopathological studies of the tissues of the root and stem of Raphanus sativus L. var. raphanistroides MAKINO after treatment with the antibiotic. Severe delayed damage was observed at 36 h after treatment with racemomycin-D, the parenchymatous cells of the treated groups contained many disintegrated fragments of cytoplasm, and the cell membrane had become much thinner. At 48 h after treatment with racemomycin-D, the amount of chlorophyll in leaves of R. sativus of the treated groups was greatly decreased as compared with the control group, and remained at a low level thereafter.View full abstractDownload PDF (1194K) -
TAKASHI OHSAWA, HIROSHI MIURA, KIYOSHI HARADA1985 Volume 33 Issue 7 Pages 2916-2923
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSA new and simple technique for the preparation of liposomes, the freeze-thawing method (FT method), was developed and evaluated for encapsulation efficiency by using L-asparaginase (A-ase) as a model drug. The encapsulation percentage of A-ase in liposomes (EN%) was determined by three methods, i.e. the measurement of free and total activities of A-ase, the gel filtration method and the trypsin treatment method. A-ase was encapsulated in FT liposomes with a higher efficiency than in liposomes prepared by the hydration method (HY liposomes), although the shape, the particle size distribution and the appearance of multilamellar structure of FT and HY liposomes were similar to each other. A-ase encapsulated in FT liposomes was resistant to proteolysis by trypsin treatment and to leakage by osmotic shrinkage. The FT method has the following advantages over the HY method for the practical preparation of liposomes as drug carriers : the use of an organic solvent or a detergent is unnecessary, sterilization can be carried out with a membrane filter and the preparation technique is simple.View full abstractDownload PDF (942K) -
TANENO KAJI, YOSHIKO HIRAI, JUTARO OKADA1985 Volume 33 Issue 7 Pages 2924-2931
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSSodium, calcium, magnesium, zinc and aluminium stearates and behenic, stearic, palmitic, myristic and lauric acids were tested as lubricants during the compaction of lactose powder. Lactose powder, lactose mixtures with lubricants and lubricant powders were compressed in a cylindrical die with flat-surfaced punches. As the upper punch pressure required to compact a given lubricant to a certain porosity increased, the pressure required for the lactose mixture with that lubricant decreased. As regards the pressure-transmission ratio, the higher the value that the lubricant powder showed, the higher the value for the lactose mixture with that lubricant. The Heckel's constants were determined, and a larger k-value (the slope of Heckel's plot at high pressure) for lubricant powder resulted in a smaller value for the mixture. It is suggested that lubricants with higher melting points (metal stearates) provide more effective lubrication on the die wall and between lactose particles than lubricants with lower melting points (fatty acids).View full abstractDownload PDF (738K) -
MASAYUKI MIZUNO, MAMI YOSHIDA, MITSURU HASHIDA, TOSHIKIRO KIMURA, HITO ...1985 Volume 33 Issue 7 Pages 2932-2940
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe contribution of intestinal mucosal lipid components to the membrane permeation process of water-soluble drugs was examined by using liposomes as a model membrane. Mucosal lipids extracted from the rat small intestine were fractionated into several lipid classes by column chromatography and each lipid fraction was reconstituted into the liposomal membrane. The release rate of drugs incorporated in liposomes was measured (pH 6.5) as an index of the membrane permeability. 6-Carboxyfluorescein (6-CF), procainamide ethobromide (PAEB) and sulfanilic acid (SA) were employed as model drugs. Their absorption percentages from rat small intestine in one hour were 2.4%, 3.2% and 7.5%, respectively, as determined by the in situ recirculation technique (pH 6.5). These drugs were more permeable through the liposomal membranes containing intestinal free fatty acids than egg lecithin liposomes, with the exception of SA. Arrhenius plots of the release rate constants indicated that increased liposomal membrane fluidity was partly responsible for this accelerated release in the case of PAEB, but no significant change was observed in the activation energy for the membrane permeation of 6-CF. From these observations, it is concluded that lipid components, especially free fatty acids of the intestinal mucosa, play an important role in the absorption process of these water-soluble drugs.View full abstractDownload PDF (880K) -
SATOSHI MATSUMOTO, YOSHIKO ARASE, YOSHINOBU TAKAKURA, MITSURU HASHIDA, ...1985 Volume 33 Issue 7 Pages 2941-2947
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSIn order to clarify the factors dominating the antitumor effects of mitomycin C-dextran conjugates (MMC-D), the plasma disposition of MMC-D in rats, and the in vivo and in vitro antitumor activities were studied in comparison with those of mitomycin C. Three types of MMC-D, conjugates with dextran having molecular weights of 10000, 70000 and 500000, were administered to rats by intravenous, intramuscular and intraperitoneal injection, and the plasma concentrations of MMC were determined by bioassay. Similar sustained plasma levels of MMC after injection of MMC-D were obtained regardless of carrier size or administration route. Intraperitoneal injection of MMC-D significantly improved the survival time of mice bearing L1210 leukemia, while intravenous or intramuscular injection did not. MMC-D showed higher maximum activity at a lower dose as its molecular size increased. L1210 leukemia cells were exposed to MMC-D for 1 h in vitro and cytocidal activities were evaluated in terms of the survival time of mice inoculated with treated cells, or the growth rate of cells in a cell culture system. MMC-D exhibited different cytocidal activities depending on its molecular weight in these systems whereas MMC-D was considered to liberate MMC at the same rate regardless of molecular weight in vitro. These results suggest that MMC-D has some direct interaction with tumor cells and this interaction plays an important role in the manifestation of antitumor activity in vivo, as well as a modified pharmacokinetic behavior in the body.View full abstractDownload PDF (724K) -
YASUO MATSUSHITA, IKUO MORIGUCHI1985 Volume 33 Issue 7 Pages 2948-2955
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSConditions and the limits of measurement for protein-binding studies by the ultracentrifugation (UC) method were investigated, and the UC method was compared with the currently used equilibrium dialysis (ED) method in terms of accuracy and reliability. Serum albumin (SA) concentrations of around 5.0×10-5 M and drugs with molecular weights of less than 400 were suitable for the UC method. The optimal rotation speed was considered to be 30000 rpm (61380×g). The UC method and ED method were compared in measurements of the binding of 4'-hydroxyazobenzene-2-carboxylate, 2-naphthoate, salicylate and warfarin to bovine SA and human SA. The UC method was confirmed to be comparable with the ED method in terms of reliability and rather superior in terms of reproducibility, especially at low drug concentrations.View full abstractDownload PDF (697K) -
TAKEO KAWAGUCHI, YOSHIKI SUZUKI, NAOKI NAMBU, TSUNEJI NAGAI1985 Volume 33 Issue 7 Pages 2956-2961
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSFive acidic 3', 5'-diesters of 5-fluoro-2'-deoxyuridine (FUdR) including 3-carboxypropionate, 4-carboxybutyrate, 5-carboxypentanoate, 6-carboxyhexanoate and 7-carboxyheptanoate were synthesized, and their susceptibility to porcine liver, rat liver homogenate, rat intestinal homogenate and rat plasma esterase preparations was studied. The susceptibility of the derivatives to porcine liver esterase preparation increased as the number of methylene groups in the ester promoiety increased in both acidic (pH 5.0) and neutral (pH 7.0) solutions. The derivatives showed about 100 times higher reactivity to the esterase at pH 5.0 than at pH 7.0. With the rat tissue homogenates and plasma preparations, the longer the ester chain the higher the susceptibility, except for 3', 5'-bis (3-carboxypropionyl) FUdR (I) with rat liver homogenate. Though the reactivity of I was the lowest with porcine liver esterase preparation and not measurable with rat intestinal homogenate and plasma, I showed the highest reactivity with the rat liver homogenate.View full abstractDownload PDF (633K) -
TADAKAZU TOKUMURA, YUKI TSUSHIMA, KIMIO TATSUISHI, MASANORI KAYANO, YO ...1985 Volume 33 Issue 7 Pages 2962-2967
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe bioavailability of cinnarizine (CN) upon oral administration of its β-cyclodextrin complex to beagle dogs was investigated in comparison with that of CN alone. The dissolution rate at pH 3.0-6.8 was increased significantly by inclusion complexation, but there was no difference in the bioavailability of CN after oral administration of β-cylodextrin complex and that of CN alone. The absorption of CN was decreased significantly when CN was administered with NaHCO3. However, no decrease was observed in the case of CN-β-cylodextrin inclusion complex.View full abstractDownload PDF (621K) -
HITOSHI SASAKI, TOSHIYUKI KAKUTANI, MITSURU HASHIDA, TOSHIKIRO KIMURA, ...1985 Volume 33 Issue 7 Pages 2968-2973
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe potential utility of lipidic dosage forms incorporating a lipophilic prodrug of mitomycin C (MMC), nonyloxycarbonyl MMC, was evaluated by determining blood levels after intramuscular and intravenous administration of different formulations. After intramuscular injection of MMC in the forms of liposomes, O/W emulsion and dimethyl sulfoxide (DMSO) solution, MMC appeared in the circulation at an early stage and disappeared rapidly regardless of dosage form. However, neither MMC nor prodrug could be detected in the blood after injection of the prodrug in lipidic dosage forms. These results suggest that formulations consisting of prodrug and lipidic carriers would show less severe systemic side effects than formulations of MMC for local injection. In the same experiment, the lipid component of liposomes was detected in the blood, but that of emulsion did not appear in the blood. On the other hand, although intravenous injection of the prodrug in DMSO solution resulted in rapid conversion to MMC, slow conversion was observed when this prodrug was administered in the form of O/W emulsion. These results suggest that the prodrug was retained in these carriers and released gradually, followed by subsequent rapid conversion to MMC in the plasma. Thus, wide potential applicability of these systems for controlling the fate of MMC was demonstrated.View full abstractDownload PDF (679K) -
EIJI MIZUTA, ATSUKO TSUBOTANI1985 Volume 33 Issue 7 Pages 2974-2982
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSDrugs administered in vivo are transferred directly or indirectly from blood to tissues or fluids, and vice versa. In this paper, we propose a model by which the drug concentration in tissues or fluids can be analyzed simply by using a transfer rate constant and apparent clearance ratio, regardless of the transfer route. By using this model, the concentration-time curves of antibiotics in pleural effusion, burn blister fluid and aqueous humor of human subjects were successfully analyzed.View full abstractDownload PDF (770K) -
AKIRA KUSAI, SEIJI TANAKA, SEIGO UEDA1985 Volume 33 Issue 7 Pages 2983-2989
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESSThe kinetics and mechanisms of the degradation of 2, 5-bis (1-aziridinyl)-1, 4-benzoquinone (I) in alcohols were investigated and compared with those in aqueous solution obtained previously. The degradation of I in alcohols follows pseudo first-order kinetics as did that in aqueous solution. Degradation rates in a series of alcohols show a good correlation with Kosower's Z-values (empirical measures of solvent polarity). Degradation mechanisms of I in alcohols were investigated in methanol, where the degradation rate of I is relatively high, being suitable for detailed study. Five compounds were observed as degradation products of I in methanol, and the degradation process of I appeared to be rather complicated. However, the degradation behavior of I and some of these five degradation products in proton-rich methanol and methylate-rich methanol allowed us to deduce the chemical structures of all the degradation products : 5-(1-aziridinyl)-2-(2-methoxyethyl) amino-1, 4-benzoquinone, 2, 5-di (2-methoxyethyl) amino-1, 4-benzoquinone, 5-(1-aziridinyl)-2-methoxy-1, 4-benzoquinone, 2, 5-dimethoxy-1, 4-benzoquinone and 5-methoxy-2-(2-methoxyethyl) amino-1, 4-benzoquinone. Their behavior also made it clear that I is degraded in methanol through a combination of two mechanisms : methanolysis of the aziridine ring, which is cleaved to a methoxyethylamino group, and substitution of the aziridine ring by a methoxy group. Therefore, the degradation mechanisms of I in methanol are concluded to be essentially the same as those in aqueous solution.View full abstractDownload PDF (622K) -
JUN OKUDA, KAYA YASHIMA, KAZUHIRO INAGAKI, ICHITOMO MIWA1985 Volume 33 Issue 7 Pages 2990-2995
Published: July 25, 1985
Released on J-STAGE: March 31, 2008
JOURNAL FREE ACCESS1-[(p-Bromophenyl) sulfonyl] hydantoin (p-Br-PSH), an inhibitor of aldose reductase, was intubated once daily at a dose of 25 or 50 mg/kg into rats fed a 50% galactose diet. Cataract formation was decreased in rats dosed with p-Br-PSH at 50 mg/kg from the first day on galactose diet relative to untreated galactosemic rats (control rats). In the groups pretreated with p-Br-PSH for 10 d before the start of galactose diet feeding, subsequent treatment with the drug markedly delayed cataract formation. Treatment with p-Br-PSH at 50 mg/kg from the first day (day 0) on galactose diet produced a statistically significant though small (<11%) decrease in the lenticular galactitol level at day 5 and 9. These results suggest that the delay of cataract formation by treatment with p-Br-PSH is caused not only by the decrease in osmotic pressure resulting from reduction in the lenticular galactitol level but also by other unknown mechanisms. Treatment with p-Br-PSH at 50 mg/kg reduced galactitol accumulation by about 50% at day 5 and 9 in the sciatic nerve and by 26% at day 26 in the retina. The sciatic nerve myo-inositol level in control rats was decreased by 42% at day 9 compared with that of normal diet fed rats. The galactosemic rats treated with p-Br-PSH at 25 and 50 mg/kg showed increases (16 and 34%, respectively) in the sciatic nerve myo-inositol level. The importance of these findings for the treatment of diabetic complications is discussed.View full abstractDownload PDF (643K)