Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 45, Issue 12
Displaying 1-44 of 44 articles from this issue
  • Yaeno ARIMA, Akihiko HATANAKA, Sachiko TSUKIHARA, Kaori FUJIMOTO, Keik ...
    1997 Volume 45 Issue 12 Pages 1881-1886
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    α-, β- and γ-Thujaplicins are three-tropolone-related compounds purified from the woods of Chamaecyparis obtusa SIEB. et ZUCC. and Thuja plicata D. DON. Based on our recent finding that β-thujaplicin inhibits the formation of sunburn cells (SBC), which appear in the epidermis after UVB irradiation, we have speculated that β-thujaplicin is a potent scavenger against active oxygen species. ESR spin-trapping, chemiluminescence and fluorescence methods, and cyclic voltammetry were used to evaluate the abilities of β-thujaplicin and its isomers, α- and γ-thujaplicins, as scavengers of five kinds of active oxygen species such as superoxide anion radicals, hydroxyl radicals, singlet oxygens, tert-butyl peroxyl radicals and hydrogen peroxides. These compounds were found to have comparable inhibitory effects of hydroxyl radicals generated by the Fenton reaction and high scavenging activities against tert-butyl peroxyl radicals as compared with those of l-ascorbic acid and dl-α-tocopherol, and α-thujaplicin was found to have the highest activity against hydrogen peroxides among the thujaplicins.However, the effects of these compounds on superoxide anion radicals and singlet oxygens were less than those of l-ascorbic acid and dl-α-tocopherol. These facts suggest that thujaplicins have effective antioxidant ability. This ability is thought to be due in part to the chelating ability and redox potential of the compounds, which in turn are related to the prevention of UV-induced photo-damage in vivo.
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  • Yasuyuki KITA, Yoshifumi TAKEDA, Takayuki OKUNO, Masahiro EGI, Kiyosei ...
    1997 Volume 45 Issue 12 Pages 1887-1890
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    A combination of PhICl2 and Pb(SCN)2 is effective for the p-selective thiocyanation of various types of p-unsubstituted phenols and naphthols 1 to give p-thiocyanatophenols and naphthols 3. The reaction proceeded at 0°C to room temperature in good to quantitative yields. Twenty-five examples are given, in which various functional groups, such as chloro, allyl, carbonyl, ester, amide, and primary hydroxyl groups, are shown to be compatible with this reaction.
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  • Takashi TANAKA, Hong ZHANG, Zhi-Hong JIANG, Isao KOUNO
    1997 Volume 45 Issue 12 Pages 1891-1897
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The hydrophobicity values of hydrolyzable tannins were evaluated by measuring the distribution of the compounds between n-octanol and water. Of 8 gallotannins 13 ellagitannins examined, pentagalloylglucose (7), the major polyphenol of Paeoniae Radix, showed the largest partition coefficient value. In aqueous solution, pentagalloylglucose associated with various crude drug constituents, such as paeoniflorin, glycyrrhizin potassium salt, aconitine trifluoroacetate, liquiritin apioside and amygdalin. The 1H-NMR spectroscopic examination suggested that the association occurred preferentially at the most hydrophobic sites of the molecules. The association with these compounds inhibited the distribution of pentagalloylglucose into the n-octanol phase and adsorption on hide powder. In addition, the water solubility of the biologically active polymeric proanthocyanidins of rhubarb was increased by association with rhein 8-O-glucoside potassium salt, the major anthraquinone glycoside of rhubarb.
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  • Koji YAMADA, Hayato IWADARE, Teruaki MUKAIYAMA
    1997 Volume 45 Issue 12 Pages 1898-1905
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Construction of the AB-ring system of the taxane framework via an A-ring annulation strategy was demonstrated by base-mediated intramolecular aldol reaction of (Z)-2, 2-dimethyl-3-(1-methyl-2-oxopropylidene)cyclooctanone, affording the title compound, 1-hydroxy-8, 11, 11-trimethylbicyclo[5.3.1]undec-7-en-9-one. A cyclization precursor, the tetra-substituted (Z)-alkene, was prepared from the corresponding cyclooctanone derivative, 3-[(α, α-dimethylbenzyl)dimethylsiloxy]-2, 2-dimethylcyclooctanone via a bicyclic α, β-unsaturated lactone intermediate.
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  • Yoshiji TAKEMOTO, Shigeo UEDA, Jun TAKEUCHI, Yasutaka BABA, Chuzo IWAT ...
    1997 Volume 45 Issue 12 Pages 1906-1909
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    By LiClO4-catalyzed cycloaddition with Danishefsky's diene 5, an optically active 1-azatriene Fe(CO)3 complex was converted into the 2-substituted dehydropiperidinone 8, from which a piperidine alkaloid 1 (SS20846A) was synthesized in an enantiomerically pure form via successive reduction and removal of the protecting groups. Although the reduction of the ketone 3 proceeded with cis-selectivity even with a hindered reducing agent, the desired trans-alcohol 4 could be obtained by the reaction with sodium borohydride in the presence of cerium(III) chloride. The cis-selective reduction of 3 originates from the equatorial attack of a hydride on conformer A, in which the diene Fe(CO)3 moeity is axially oriented due to the severe steric hindrance with the p-methoxyphenyl (PMP) group on the nitrogen atom. However, the cerium salt reverses the stereoselectivity of the hydride reduction of 3.
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  • Hui Li ZHANG, Akito NAGATSU, Toshihiro WATANABE, SAKAKIBARA, Harumi O ...
    1997 Volume 45 Issue 12 Pages 1910-1914
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Seven antioxidative serotonin derivatives were isolated from safflower (Carthamus tinctorius L.) oil cake. Their structures were established as N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]ferulamide (1), N-[2-(5-hydroxy-1H-indol-3-yl)ethyl]-p-coumaramide (2), N, N'-[2, 2'-(5, 5'-dihydroxy-4, 4'-bi-1H-indol-3, 3'-yl)diethyl]-di-p-coumaramide (3, ) N-[2-[3'-[2-(p-coumaramido)ethyl]-5, 5'-dihydroxy-4, 4'-bi-1H-indol-3-yl]ethyl]ferulamide (4), and N, N'-[2, 2'-(5, 5'-dihydroxy-4, 4'-bi-1H-indol-3, 3'-yl)diethyl]-diferulamide (5), N-[2-[5-(β-D-glucosyloxy)-1H-indol-3-yl]ethyl]-p-coumaramide (6), and N-[2-[5-(β-D-glucosyloxy)-1H-indol-3-yl]ethyl]ferulamide (7). Antioxidative activities of the compounds were measured by the ferric thiocyanate method and the α, α-diphenyl-β-picrylhydrazyl (DPPH) method, and compounds 1-5 were found to have relatively strong antioxidative activity.
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  • Takashi TANAKA, Zhi-Hong JIANG, Isao KOUNO
    1997 Volume 45 Issue 12 Pages 1915-1921
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Seven novel ellagitannins named rhoipteleanin A-G were isolated from the fruits of Rhoiptelea chiliantha and their structures were unequivocally established on the basis of spectroscopic and chemical evidence. In the molecules of rhoipteleanin A-F, (S, S)-flavogallonyl esters spanned two glucopyranose moieties; hence, these tannins represent the first dimeric ellagitannins generated by stereospecific intermolecular C-C oxidative coupling between the galloyl and hexahydroxydiphenoyl groups. The change in the 1H-NMR chemical shifts of specific proton signals of 1(β)-O-galloylpedunculagin, the biogenetic precursor of rhoipteleanin A, in dueterium oxide at various concentrations suggested that the stereochemically regulated hydrophobic interaction between two molecules of the precursor restricts the intermolecular C-C coupling to S-biphenyl bond formation.
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  • Shin-ichi YAMADA, Ryuzo YOSHIOKO, Takeji SHIBATANI
    1997 Volume 45 Issue 12 Pages 1922-1927
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Practical preparation methods of an optically active intermediate of diltiazem, (+)-(2S, 3S)-5-[2-(dimethylamino)ethyl]-2, 3-dihydro-3-hydroxy-2-(4-methoxyphenyl)-1, 5-benzothiazepin-4(5H)-one [(+)-7], have been developed by the use of physicochemical and chemical resolutions. 1) The salt of (±)-7 with 3-amino-4-hydroxy-benzenesulfonic acid (AHS), was found to exist as a conglomerate and could be reproducibly resolved into (+)-7·AHS and (-)-7·AHS of 94-98% ee by a preferential crystallization procedure. 2) (+)-(1R)-3-Bromocamphor-9-sulfonic acid [(+)-BCS] was found to be an efficient resolving agent for (±)-7 and the diasteoremeric resolution provided (+)-7·(+)-BCS·2H2O salt in >43% yield and >97% ee by fractional crystallization. It is presumed that the crystal water of (+)-7·(+)-BCS·2H2O plays an important role in the selective crystallization during this efficient resolution.
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  • Koichi MACHIDA, Masao KIKUCHI
    1997 Volume 45 Issue 12 Pages 1928-1931
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Six new triterpenoids, viburnols F, G, H, I, J and K, were isolated from the leaves of Viburnum dilatatum THUNB. (Caprifoliaceae). The structures were determined by extensive spectroscopic studies. Viburnols F, G and I are the first example of a new class of modified dammarane-type triterpenes.
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  • Takeaki NAITO, Yuko HONDA, Vanida BHAVAKUL, Sayaka YAMAGUCHI, Azusa FU ...
    1997 Volume 45 Issue 12 Pages 1932-1939
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    (±)-Anantine, (±)-isoanatine and related compounds were synthesized via two key reactions, sulfanyl radical addition-cyclization and stereoselective construction of the E-benzylidene moiety.
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  • Tetsushi YAMASHITA, Eiji TSURU, Eri BANJYO, Matsumi DOE, Kozo SHIBATA, ...
    1997 Volume 45 Issue 12 Pages 1940-1944
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Enantiomeric piperazin-2-one derivatives, N, N'-ethylene-bridged alanylphenylalanines (1a or 1b), were synthesized using (S)- or (R)-alanine and phenylalanine as starting materials, and were inserted into the second and third positions of enantiomeric pseudo-tetrapeptides (P1a- or P1b-OEt). The corresponding piperazine derivatives (1a-or 1b-sRed) obtained by selective BH3 reduction of the amide carbonyl groups of 1a or 1b were similarly inserted into the same positions of tetrapeptides (P1a- and P1b-sRed). Enantiomeric N, N'-ethylene-bridged tyrosyltyrosine derivatives (2a or 2b) obtained from (S)- or (R)-tyrosine were also inserted into the first and second positions of two pairs of enantiomeric tetrapeptides (P2a- and P2b-OEt or P'2a- and P'2b-OEt). The opiate activities of the eight peptides thus obtained were studied by use of the mouse vas deferens and the guinea pig ileum assays in order to elucidate the structure-activity relationships of these peptides, especially with respect to stereochemistry.
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  • Koichi HOMMA, Tatsuya WATANABE, Toru IIJIMA, Michihisa YATO, Kenji MAT ...
    1997 Volume 45 Issue 12 Pages 1945-1954
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    A series of 2-aryl-4, 5-dihydro-1H-thieno[3, 2-e]benzimidazoles (1, 2) was prepared by condensation of 5-acylamino-4, 5, 6, 7-tetrahydrobenzo[b]thiophen-4-ones (9, 10) with ammonium acetate under azeotropic reaction conditions. Various congeners, N-methyl and N-phenyl analogues (3-5), 4, 5-dihydro-1H-thieno[2, 3-e]benzimidazoles (6), 4, 5-dihydro-1H-thieno[2, 3-g]benzoxazoles (7), and 4, 5-dihydro-1H-thieno[2, 3-g]benzothiazoles (8), were also prepared. Several compounds in this series were shown to be K+-competitive inhibitors of the gastric (H+/K+)-ATPase and more potent inhibitors than SK&F-96067, 3-butyryl-8-methoxy-4-(2-tolylamino)quinoline, on pentagastrin-stimulated acid secretion in chronic gastric fistula rats after intraduodenal administration.
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  • Masateru ONO, Fumiko HONDA(nee YAMADA), Ariaki KARAHASHI, Toshio KAWAS ...
    1997 Volume 45 Issue 12 Pages 1955-1960
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Alkaline hydrolysis of the ether-soluble resin glycoside fraction of seeds of Quamoclit (Q.) x multifica, a hybrid between Q. pinnata and Q. coccinea, gave new glycosidic acids, multifidinic acids A and B, along with two known glycosidic acids, quamoclinic acid A and operculinic acid A, and three organic acids, (2S)-2-methylbutyric acid, n-decanoic acid and n-dodecanoic acid. Further, as major ether-soluble resin glycosides, new jalapins named multifidins I and II, were isolated accompanied by quamoclins I-IV, which were previously obtained from seeds of Q. pinnata. The structures of multifidins I and II, and multifidinic acids A and B have been determined on the basis of chemical and spectral data.
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  • Tamaki JIKYO, Masashi ETO, Kazunobu HARANO
    1997 Volume 45 Issue 12 Pages 1961-1969
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Cycloaddition of 2, 5-disubstituted-3, 4-diphenylcyclopentadienone with acyclic conjugated dienes gave the endo [4+2]π cycloadducts, which then underwent [3, 3]-sigmatropic rearrangement to give the corresponding endo [2+4]π cycloadduct on heating at 110°C. Pyrolysis of the endo [4+2]π cycloadducts at 170°C resulted in decarbonylation to give the double Diels-Alder adduct. The sequential pericyclic reaction behavior is discussed on the basis of X-ray diffraction analyses and molecular orbital calculation data.
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  • Kiyo OKAZAKI, Takuya MAEDA, Hideaki NAGAMUNE, Yuki MANABE, Hiroki KOUR ...
    1997 Volume 45 Issue 12 Pages 1970-1974
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Bis-quaternary ammonium compounds (bis-QACs), 4, 4'-(α, ω-polymethylenedithio)bis(1-alkylpyridinium iodide)s (4DTBP-m, n), which have 3 to 10 carbon atoms in the connecting methylene chain (m) and 8 to 18 carbon atoms of the N-alkyl chain (n), were synthesized. 4DTBP-6, 12 exhibited a wide antimicrobial spectrum against gram-positive and gram-negative bacteria and fungi. The activity was stronger than those of N-dodecylpyridinium iodide (P-12), benzyldodecyldimethylammonium chloride and 2-(4-thiazolyl)benzimidazole. The bactericidal activities of 4DTBP-m, n were scarcely affected by the lengths of the alkyl chain and methylene chain. The bis-QAC that showed the highest activity was 4DTBP-6, 8 (nimimum inhibitory concentration (MIC)=1.6 μM, minimum bactericidal concentration (MBC)=2.6 μM), and its activity was about 10 times that of N-hexadecylpyridinium iodide (P-16), which was the most active in the P-n series. In addition, 4DTBP-6, 12 showed a high bactericidal activity in the ranges of pH 5 to 8.5 and 10 to 40°C, in contrast to mono-QACs. The bis-QACs synthesized in this study have excellent bactericidal properties.
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  • Takeshi YAMAMOTO, Manabu HORI, Ikuo WATANABE, Hisayoshi TSUTSUI, Kengo ...
    1997 Volume 45 Issue 12 Pages 1975-1983
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Inhibitiion of the Na/H exchanger is promising approach for treating ischemia-reperfusion injury, but no clinical agent is yet available. Recently, we established the structural requirements for potent inhibitors of the Na/H exchanger. In the present work, we designed N-(3-oxo-3, 4-dihydro-2H-benzo[1, 4]oxazine-7-carbonyl)guanidine 3a as a new lead compound for potent inhibitors with good water-solubility, based on the previous information. During the structural optimization, care was taken to keep the hydrophobicity (clogP) in the range of about 1.5-2.0, which is considered optimum for good bioavailability. Various derivatives of 3a were synthesized and the quantitative structure-activity relationship (QSAR) was studied. The QSAR result indicated that the lengths of the substituents at the 2- and the 4-positions of the 2H-benzo[1, 4]oxazine ring are parabolically related to activity. The most potent compounds were (R) and/or (S)-N-(2-ethyl-4-isopropyl(or ethyl)-3-oxo-3, 4-dihydro-2H-benzo[1, 4]oxazine-7-carbonyl)guanidines 3q-t with IC50 values of 0.036-0.073 μM. The water-solubility of the hydrochlorides and methanesulfonates is 3-5 mg/ml, which is sufficient for therapeutic use.
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  • Kenji ARAKAWA, Masanori INAMASU, Mamoru MATSUMOTO, Kunihito OKUMURA, K ...
    1997 Volume 45 Issue 12 Pages 1984-1993
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    A new series of benzoxazole 2, 4-thiazolidinediones was synthesized and evaluated for hypoglycemic activity in genetically obese and diabetic yellow KK mice. 2-Arymethyl- and 2-(heteroarhylmethyl)benzoxazole derivatives showed far more potent activity than known 2, 4-thiazolidinedione derivatives such as ciglitazone, troglitazone and pioglitazone. A facile synthesis of benzoxazole 2, 4-thiazolidinediones was also established using aminophenol 2, 4-thiazolidinedione (11) as a key intermediate. Details of synthesis and structure-activity relationships for this series are described.
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  • Tuyshi MAEKAWA, Satoshi YAMAMOTO, Yumiko IGATA, Shota IKEDA, Toshifumi ...
    1997 Volume 45 Issue 12 Pages 1994-2004
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The search for novel K+ channel openers with a non-benzopyran skeleton, unlike cromakalim, led to the discovery of a new series of (Z)-2-(α-alkoxyimino)benzylpyridine derivatives. Synthesis was achieved by using a (Z)-dominant condensation reaction of benzoylpyridines with O-alkylhydroxylamines, followed by m-chloroperbenzoic acid (m-CPBA) oxidation. The compounds were tested for thier vasorelaxant activity in tetraethylammonium chloride (TEA) and BaCl2- and high KCl-induced contration of rat aorta to identify potential K+ channel openers, and also for their effects of the coronary blood flow (CBF) after intracoronary injection in anesthetized dogs. A large number of the 2-(α-alkoxyimino)benzylpyridines strongly inhibited TEA and BaCl2-induced contraction, had no effect on 80 mM KCl-induced contraction, and increased the CBF to more than 200% of the basal flow at 10-30 μg/dog. In particular, (Z)-2-[5-bromo-α-(tert-butoxyimino)-4-fluoro-2-hydroxybenzyl]-3-hydroxypyridine 1-oxide (7d) showed highly potent vasorelaxant activity (EC50=0.28 μM) comparable to that of levcromakalim (EC50=0.17 μM), and gave a significantly longer-lasting increase (T1/2=30 min) in the CBF compared to levromakalim, nicorandil, nitroglycerin, or diltiazem (T1/2=5.2, 0.9, 0.4, and 2.2 min, respectively). It also exhibited a stable and long-lasting hypotensive effect (over 7 h) upon oral administration of 1 mg/kg in spontaneously hypertensive rats (SHRs).
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  • Kazuya YOSHIZUMI, Shoji IKEDA, Noriyasu NISHIMURA, Kohichiro YOSHINO
    1997 Volume 45 Issue 12 Pages 2005-2010
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    In our series of studies on potassium channel openers, several thienylcyanoguanidine derivatives synthesized and evaluated for smooth muscle relaxation activity in vitro. Among the newly synthesized compounds, N-cyano-N'-(5-cyano-3-thienyl)-N"-tert-pentylguanidine (4b) and N-(5-bromo-3-thienyl)-N'-cyano-N"-tert-pentylguanidine (4f) exhibited excellent activity which was proved to be based on potassium channel-opening action. Bioisosterism between benzene and thiophene ring was observed in the arylcyanoguanidines. After intravenous administration to dogs, 4b lowered the blood pressure more strougly than pinacidil.
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  • Yasuo TAKEUCHI, Ikuo WATANABE, Keiji MISUMI, Mari IRIE, Yoko HIROSE, K ...
    1997 Volume 45 Issue 12 Pages 2011-2015
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Several congeners (1b-g), with novel substituents on the benzene ring of griseofulvin, were prepared by the application of a synthetic method developed by us. Antifungal activity of these congeners decreased in order of dl-griseofulvin (1a)=1d>1b, c»1e-f (inactive). The relationship between the antifungal activity and the position or kind of substituents on the benzene ring of griseofulvin is discussed.
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  • Toshihiro AKIHISA, Ken YASUKAWA, Yumiko KIMURA, Sei-ichi TAKASE, Sakae ...
    1997 Volume 45 Issue 12 Pages 2016-2023
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The nonsaponifiable lipids of camellia and sasanqua oils from the seeds of Camellia japonica L. and C. sasanqua THUNB., respectively, were investigated for their triterpene alcohol constituents. This led to the isolation of twenty-seven triterpene alcohols of which seven were novel naturally occurring compunds, tirucalla-5, 7, 24-trien-3β-ol (1), lemmaphylla-7, 21-dien-3β-ol (2), isoeuphol (3), isotirucallol (4), (24R)-24, 25-epoxybutyrospermol (5) and its 24S-epimer (6), and isoaglaiol (7). The structures were determined by spectroscopic and chemical methods. The inhibitory effects of 3, 4, a mixture of 5 and 6, a mixture of 7 and its 24S-epimer (aglaiol), and eight known triterpene alcohols isolated in this study were evaluated in ear inflammation in mice induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The 50% inhibitory dose of these triterpenes for TPA-induced inflammation (1 μg per ear) was 0.2-0.9 mg/ear.
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  • Yuji YAMAUCHI, Hatsuo MAEDA, Hidenobu OHMORI
    1997 Volume 45 Issue 12 Pages 2024-2028
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Electrochemical polymerization of 4-(3-hydroxyphenylacetyamino)-2, 2, 6, 6-tetramethylpiperidinyl-1-oxyl (1) as a tool to immobilize 2, 2, 6, 6-tetramethylpiperidinyl-1-oxyl (TEMPO) to the surface of a glassy carbon (GC) electrode has been examined. Voltammetric studies showed that anodic treatment in H2O-MeCN (4 : 1) containing 1, NaHCO3, and NaClO4 with cycled or constant potentials provides access to a GC electrode coated with a poly(phenylene oxide) film containing immobilize TEMPO, which functions well as a catalyst for the electrochemical oxidation of alcohols. The TEMPO-modified electrode was applied to flow injection analysis (FIA) of alcohols and carbohydrates with an amperometric mode at a low applied potential. The results of FIAs demonstrated that reproducible and stable responses in the present system are obtained, not for hydrophobic alcohols, but for hydrophilic ones such as carbohydrates, although the former will be detected with a higher sensivity than the latter. The observed phenomena seem to originate from the interaction of both alcohols and their oxidized products with the hydrophobic poly(phenylene oxide) film on the electrode surface.
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  • Toshio MIYASE, Chizuru HORIKOSHI, Sachiyo YABE, Setsuko MIYASAKA, Faro ...
    1997 Volume 45 Issue 12 Pages 2029-2033
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    From the aerial parts of Verbascum (V.) sinaiticum, V. thapsiforme, V. fruticulosum and Celsia roripifoila, seven new saikosaponin homologues, called mulleinsaponins I-VII, having 13, 28-epoxy-olean-11-ene skelton were isolated together with eight known saikosaponin homologues, 3-O-β-D-fucopyranosyl saikogenin F, saikosaponn a, desrhamnosylverbascosaponin, songarosaponins C, D, mimengoside A and buddlejasaponins I, IV. The sturectures of mulleinsaponins I-VII were characterized as 3-O-β-D-glucopyranosyl-(1→3)-β-D-fucopyranosyl-6-deoxy-saikogenin F, 3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-β-D-fucopyranosyl-16-deoxysaikogenin F, 3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-β-D-fucopyranosyl-saikogenin F, 3-O-α-L-rhamno-pyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl-21β-hydroxysaiko-genin F, 3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl-21β-acetoxysaikogenin F, 3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosyl-16β-acetoxysaikogenin F and 3-O-α-L-rhamnopyranosyl-(1→4)-β-D-glucopyranosyl-(1→3)-[β-D-glucopyranosyl-(1→2)]-β-D-fucopyranosylsaikogenin F 16-O-β-D-glucopyranoside, respectively, from chemical and spectroscopic evidence.
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  • Masayuki YOSHIKAWA, Toshiyuki MURAKAMI, Hisashi MATSUDA
    1997 Volume 45 Issue 12 Pages 2034-2038
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Following the characterization of gymnemosides-a and -b, new triterpene glycosides, gymnemosides-c, -d, -e, and -f, were isolated from the leaves of Gymnema (G.) sylvestre R. BR. Their chemical structures were elucidated on the basis of chemical and physicochemical evidence as follows : 21-O-benzoyl-28-O-acetylgymnemagenin 3-O-β-D-glycopyranosiduronic acid (gymnemoside-c), 23-O-[β-D-xylopyranosyl (1→6)-β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl] gymnestrogenin (gymnemoside-d), 23-O-[β-D-xylopyranosyl (1→6)β-D-glopyranosyl (1→6)-β-D-glucopyranosyl]-28-O-[β-D-glucopyranosyl (1→6)-β-D-glyucopyranosyl] 23-hydoxylongispinogenin (gymnemoside-e), 23-O-[β-D-xylopyranosyl (1→6)-β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl]-28-O-[β-D-glucopyranosyl (1→6)-β-D-glucopyranosyl] 3β, 16β, 23, 28-tetrahydroxyolean-18-ene (gymnemoside-f). The inhibitory effects of gymnemosides-c, -d, -e, and -f and principal triterpene glycosides from G. sylvestre on glucose uptake in rat small intestinal fragments were examined, and glymnemic acids II, III, and IV, gymnemasaponin V, and gymnemoside-f were found to exhibit the inhibitory activity.
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  • Satoru WATANO, Kengo ANDO, Kei MIYANAMI, Yoshinori II, Seiei SASATANI
    1997 Volume 45 Issue 12 Pages 2039-2042
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Core particles used for aqueous film coating were prepared by agitation fluidized bed granulation, and effect of the damping speed on the granule properties of mass median diameter, geometric standard deviation, apparent density, yield friability and specific surface area were investigated. Film coating by an aqueous acylic copolymer (Eudragit NE-30D) was carried out using the core particles granulated under three levels of damping speeds, and the drug release properties of each coated product were identified. Relationship between properties of core particles and the release properties were clarified and the optimal granulation conditions to make optimal core particles for film coating were determined.
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  • Masahito MIYAMOTO, Hideki ICHIKAWA, Yoshinobu FUKUMORI, Yasuyuki AKINE ...
    1997 Volume 45 Issue 12 Pages 2043-2050
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Gadolinium (Gd)-containing microcapsules designed for neutron-capture therapy (NCT) were prepared by a spouted bed coating process. Microcapsules were designed as Gd-reservoir. They were prepared with the following properties : particle size was smaller than 50 μm, Gd-content was as high as possible, and release of Gd was suppressed as long as possible. Calcium carbonate (20-32 μm) was selected as a seed particle. As a Gd-source, gadolinium diethylenetriaminepentaacetic acid (Gd-DTPA) or a synthesized water-insoluble Gd-DTPA derivative, Gd-DTPA-distearylamide (Gd-DTPA-SA), was layered onto the seed particles. The release-suppressing layer was composed of aqueous acrylic latex of 9 : 9 : 4 poly(ethyl acrylate/methyl methacrylate/2-hydroxyethyl methacrylate). In preliminary studies, Gd/DTPA microcapsules with 41-45 μm (mass median diameter) were prepared; they released Gd with a short lag-time and 3 h-prolongation. Complete release suppression was, however, difficult to achieve because of high water-solubility of Gd-DTPA. Hence, a hydrophobic derivative, Gd-DTPA-SA, was next used as a Gd source. Gd-DTPA-SA microcapsules could be prepared with a mass median diameter of 52 μm. Gd-DTPA-SA content of the microcapsulles was 38% and release of Gd was suppressed to less than 0.2% over 60 d.
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  • Yoshiteru WATANABE, Naoki UTOGUCHI, Chisato KIMURA, Yukiko TAI, Noriyo ...
    1997 Volume 45 Issue 12 Pages 2051-2054
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The interaction between a sodium-type synthetic mica (Na-TSM), a material of reactive layered compounds which exhibit characteristic light scattering, and some aminobenzoic acid derivatives which act as UV absorbing agents (UV absorber), was investigated. Due to the observed elongation of interlayer spacing (increase in the d-value) by X-ray diffraction analysis, it was found that the powdered form of 4-aminobenzoic acid ethyl ester (4-ABE) interacts with Na-TSM, and can be immobilized in the interlayer space of Na-TSM. Consequently, an intercalation compound of 4-ABE and Na-TSM was obtained. The formation of the intercalation compound of 4-ABE and Na-TSM was accelerated by heat processing, particularly at temperatures exceeding the melting point of 4-ABE. When 2-aminobenzoic acid methyl ester (2-ABM) in liquid form at room temperature was used instead of 4-ABE, the intercalation compound of 2-ABM and Na-TSM was formed in a similar manner to that of 4-ABM and Na-TSM. The heat processing again accelerated the formation of the intercalation compound of 2-ABM and Na-TSM. Interestingly, a difference in the formation behavior of intercalation compunds between 4-ABE and 2-ABM was observed. The intercalation compound of Na-TSM and 4-ABE or 2-ABM showed efficient UV absorption in the UVB and UVA wavelength regions. Therefore, application of a layered compound of Na-TSM and 4-ABE or 2-ABM as a novel UV screening system is promising.
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  • Mei-Lin GO, Tong-Lan NGIAM
    1997 Volume 45 Issue 12 Pages 2055-2060
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The antimalarial drug mefloquine binds avidly to phospholipids in biomembranes. The thermodynamics of the partitioning process in dimyristoylphosphatidylcholine (DMPC) bilayers was investigated to give insight into the drug-phospholipid interaction. Thermodynamic parameters for the partition equilibria were evaluated from the equilibrium partition coefficients measured as a function of temperature. Negative values of ΔH and ΔS were obtained for the transfer of mefloquine from the aqueous to the gel phase of the phospholipid. The partitioning is enthalpy controlled which suggests that mefloquine interacts strongly with the phospholipid phase. In contrast, the partitioning of mefloquine into the liquid crystalline phase of DMPC is entropy controlled which is typical of a hydrophobic interaction between mefloquine and the aqueous phase. The partitioning of mefloquine into the bulk solvents octanol and hexane were found to be enthalpy and entropy controlled, respectively. The enthalpy dominated partitioning of mefloquine into gel phase DMPC and octanol is attributed to the occurrence of hydrogen bonding and van der Waals interactions between solute and solvent. The flat shape of mefloquine may further its interaction with the orderly domains of the lipidic/organic phase. This is apparent from a comparison of the partitioning characteristics of another structurally related but conformationally different molecule, quinine into DMPC and octanol.
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  • Kaori JONO, Hideki ICHIKAWA, Yoshinobu FUKUMORI, Ryuichi KANAMORI, Yas ...
    1997 Volume 45 Issue 12 Pages 2061-2075
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Microcapsules whose membranes contained soybean lecithin (SL), cholesterol (CH), stearic acid (SA) and polyvinylpyrrolidone (PVP) at various compositions were prepared. Then, dissolution and swelling behaviors of the microcapsules in a 0.9% saline solution were studied to be related to the phase diagram of three components containing 42% of PVP in anhydrous state. In the aqueous solution, when an anhydrous microcapsule membrane was composed of SL not saturated with both CH and SA, the microcapsules showed rapid release of carbazochrome sodium sulfonate (CCSS, a model drug), poor particle-swelling and spouting of droplets containing CCSS. Long-delayed relase of CCSS and drastic particle-swelling with no spouting of droplets were observed when the anhydrous membrane was composed of SL saturated with both CH and SA and the composition was not close to the two-component line, CH-SA, or to the saturation line. The spounting of droplets would be attributable to the CH and/or SA-poor SL phase and to the SL phase which dissolved CH and SA, but contained either CH or SA only in a small amount, and the delayed relase would be due to the CH and SA-rich SL phase dissoleving a great amount of CH and SA formed by hydration. The degree of release suppression and particle-swelling depended on the SL content. At 20-45% of SL content, the prologed-release, great particle-swelling and no spouting of drolets at the early stage were observed only when the CH and SA-rich SL phase formed by hydration contained a high content of CH and SA.
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  • Kazunobu YOSHIHARA, Izumi TANEMURA, Yoshihiro SAITO, Haruhisa UEDA, Ta ...
    1997 Volume 45 Issue 12 Pages 2076-2078
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The stability constants for the inclusion of alkanediol compounds with α-cyclodexitrin (α-CyD) in aqueous solution have been determined by a competitive method using static head-space gas chromatography (SHSGC). The stability constants obtained by this method were in agreement with those obtained by the calorimetry method. The competitive method is applicable to the low volatile guest-CyD systems. Therefore, it was concluded that the competitive SHSGC measurement is another useful means of determining the stability constants of complex formation in an aqueous solution.
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  • William A. HEWLETT, Tomas DE PAULIS, N. Scott MASON, Dennis E. SCHMIDT ...
    1997 Volume 45 Issue 12 Pages 2079-2084
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    We report an improved synthesis of unlabeled (S)-iodozacopride, the radiolabeling of (S)-[125I]iodozacopride via deschloro-(S)-zacopride, and a re-evaluation of its affinity for the 5-HT3 receptor. Unlabeled (S)-iodozacopride was prepared in seven steps from 4-aminosalicylic acid via alkaline hydrolysis of its 4-acetamide derivative. Catalytic hydrogenation of (S)-iodozacopride gave deschloro-(S)-zacopride, identical to the obtained from (S)-3-amino-quinuclidine and 4-amino-2-methoxybenzoic acid via its corresponding 1-imidazole derivative. Radioiodination to produce (S)-[125I]idozacopride was accomplished by treatment of deschloro-(S)-zacopride with 5 mCi sodium 125iodide and chloramine-T in hydrochloric acid. Purification of the reaction products using an HPLC system capable of detecting chlorinated side-products revealed a mixture of 2.1 mCi (1.3 nmol) (S)-[125I]idozacopride and (S)-zacopride (1.5 nmol). Saturation analysis of the binding of the purified (S)-[125I]iodozacopride to whole rat brain homogenates gave an estimated KD of 1.10±0.07 nM. As anticipated, this is approximately half the KD reported for binding of racemic [125I]iodozacopride, and differs from the previosuly reported values by an order of magnitude. Analysis of the apparent binding affinity of a 1 : 1 mixture of (S)-[125I]iodozacopride and (S)-zacopride suggests that the previous result may have been confounded by contamination of the product with unlabeled (S)-zacopride. Competition analysis of the displacement of the displacement of (S)-[125I]iodozacopride binding by unlabeled (S)-iodozacopride and (S)-zacopride gave Ki values of 0.95 and 0.21 nM, respectively.
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  • Hiroyuki AKITA, Keisuke KATO, Isao UMEZAWA, Hiroko MATSUKURA
    1997 Volume 45 Issue 12 Pages 2085-2088
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Neutral amphiphiles of a new type corresponding to 1, 2-dialkylated mannitol ethers (6-10) were synthesized. Amephiphile-lipase aggregates were found to function as an immobilized enzyme system for enantioselective acetylation or enantioselective hydrolysis of α-hydroxy esters or α-acetoxy esters, respectively, in organic solvents.
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  • Eiichi KOTANI, Tetsuya TAKEYA, Hideaki SHIMIZU, Hirotaka EGAWA, Takesh ...
    1997 Volume 45 Issue 12 Pages 2089-2092
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Oxidation of N, N-dimethylaniline (1) utilizing the Fe(PA)3/H2O2/MeCN system and the Fe(ClO4)3·9H2O/PHA-Py/H2O2/MeCN system, simple model systems for mono-oxygenases, in the presence of acetic anhydride (Ac2O) afforded predominantly the N-acetylative demethylation product, N-methylacetanilide (4), along with a few other compounds.
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  • Kouichi UOTO, Haruhiro TAKENOSHITA, Takashi ISHIYAMA, Hirofumi TERASAW ...
    1997 Volume 45 Issue 12 Pages 2093-2095
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    We have developed a new method to modify the C-4 position of 10-deacetylbaccatin III (5) using the C-4 acetoxy anion of the 13-keto derivative (7) and various alkyl halides. The method developed herein shound be very useful for the preparation of C-4 modified taxoid analogs.
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  • Yasuo TAKEUCHI, Masayuki KITAOMO, Ming-rong CHANG, Shota SHIRASAKA, Ch ...
    1997 Volume 45 Issue 12 Pages 2096-2099
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Indolo[3, 2-b]quinoline derivatives (1b-i) with a methyl group at each possible position have been synthesized. The 1-methyl (1b) and 9-methyl (1i) derivatives were inactive, but the 3-methyl (1d), 4-methyl (1e), and 6-methyl (1f) derivatives exhibited high treatment/control (T/C) value and cure rates against leukemia P388 in mice. These results indicated that modification of indolo[3, 2-b]quinoline derivatives at 3, 4, and 6 positions may be useful approach for lead optimization.
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  • Kailasam SRIVIDYA, Natesan BALASUBRAMANIAN
    1997 Volume 45 Issue 12 Pages 2100-2103
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    An indirect, sensitive spectrophotometric method for the assay of thiamine is described. The procedure is based on the formation of a mercaptide by thiamine, with a known excess of silver ions in a buffered medium of pH 9.0±0.1. The unreacted silver ions are determined by the formation of an ion-pair complex with 1, 10-phenanthroline and 2, 4, 5, 7-tetrabromofluorescein, which shows an absorption maximum at 550 nm. The absorbance is found to decrease linearly with increasing concentrations of thiamine, which is corroborated by the calculated correlation coefficient value of -0.998. The system obeys Beer's law for 0-25 μg of thiamine in an overall aqueous valume of 10 ml. The molar absorptivity and relative standard deviation (RSD) were calculated to be 7.8×104 lmol-1 cm-1 and 2.5% (n=10), respectively. The proposed method was applied successfully to the determination of thiamine in pharmaceutical preparations. The reliability of the assay was established by parallel determination by the standard thiochrome method and recovery studies.
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  • Shoko YOKOYAMA
    1997 Volume 45 Issue 12 Pages 2104-2106
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The surface potential (Δψ) of the mixed micelles composed of dibucaine hydrochloride (DC) and nonionic heptaethylene glycol dodecyl ether (HED) has been estimated by measuring the fluorescence intensity of ammonium 8-anilino-1-naphthalenesulfonate (ANS) as a fluorescent probe. The value of +Δψ increases with an increasing mole fraction of DC (XDC) and decreases with increasing ionic strength (I). These changes are due to the effects of the ositive charge of DC and of the ionic atmosphere of Cl-, respectively. Surface charge density (σ) was, therefore, determined from Δψ according to the Gouy-Chapman theory, with a results that σ is nearly independent of I and proportional to XDC. These results have led to a conclusion that the state of the diffuse layer surrounding the Stern layer at the micelle surface is represented well by the Gouy-Chapman theory.
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  • Susumu ISHIMITSU, Ikuko MISHIMA, Sumiko TSUJI, Tadashi SHIBATA
    1997 Volume 45 Issue 12 Pages 2107-2109
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Photo-illumination of riboflavin sodium phosphate (Rp) with phenylalanine produced significant levels of o-tyrosine, m-tyrosine and p-tyrosine as hydroxylated products. The hydroxylation of Rp was pH-dependent, and the maximum rate was around pH 4.5. Replacement of air with nitrogen prevented the formation of tyrosine isomers while the addition of superoxide dismutase or catalase to this system prevented hydroxylation. The tyrosine formation by the system was significantly prevented by hydroxyl radical (HO·) scavengers such as potassium iodide, potassium bromide, thiourea and sodium formate. No free iron and cupric ions were detected in the reaction mixture by inductively-coupled plasma atomic emission spectrometry. Tha above results suggest that the formation of HO· may occur in the photochemical reactoin system in the presence of Rp under aerobic conditions, and that a superoxide radical and hydrogen peroxide may be involved in HO· formation.
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  • Tadayuki UNO, Mayumi TSUJI, Mika SHOJI, Michiyo SHIKISHIMA, Saburo SHI ...
    1997 Volume 45 Issue 12 Pages 2110-2112
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The adenine base was liberated by the oxidative cleavage of the N-glycosidic bond of substrates (5'- and 3'-AMP, 5'- and 3'-dAMP) in the hemin-cumene hydroperoxide system, which was accelerated in the presence of 1-methylimidazole.
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  • Koji YAMADA, Takashi TOZAWA, Katsuyuki SAITOH, Teruaki MUKAIYAMA
    1997 Volume 45 Issue 12 Pages 2113-2115
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Stereoselective syntheses of ω-(α-bromoketo) octanals and nonanal with oxygenated functions and formation of the corresponding eight-membered carbocyclic aldols by subsequent samarium(II)-mediated cyclization are demonstrated. Cyclooctenones deoxygenated at the C2 or C10 position in the taxane framework are prepared by dehydration of the above aldols.
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  • Tomohiko KAWATE, Natsuko FUKUTA, Atsushi NISHIDA, Masako NAKAGAWA
    1997 Volume 45 Issue 12 Pages 2116-2118
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Both enantiomers of 3-deoxysphingosine as well as their cis-isomers were synthesized stereoselectively from L- and D-serine.
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  • Masao TOYOTA, Alicia BARDON, Norma KAMIYA, Shigeru TAKAOKA, Yoshinori ...
    1997 Volume 45 Issue 12 Pages 2119-2121
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    The diethyl ether extract of the Argentina liverwort Dumortiera hirsuta yielded a sesquiterpenoid with a novel carbon skeleton. The structure was estalished by extensive 2D NMR techniques and X-ray crystallographic analysis. It was shown to be 3, 4, 11-trimethyl-7-methylenebicyclo [6. 3. 0] undec-2-en-11α-ol.
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  • Jun-ichi MATSUO, Kenji KOGA
    1997 Volume 45 Issue 12 Pages 2122-2124
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Enantioselective alkylation at the α-position of phenylacetic acid (1) can be realized in up to 68% ee by treating the dilithiated 1 with alkyl halides in the presence of a chiral bidentate lithium amide ((R)-3).
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  • Yasuhiro NISHIYAMA, Tsutomu MURAKAMI, Keisuke KURITA, Naoki YAMAMOTO
    1997 Volume 45 Issue 12 Pages 2125-2127
    Published: December 15, 1997
    Released on J-STAGE: March 31, 2008
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    Five peptides corresponding to the amino-terminal sequence of RANTES (regulated upon activation, normal T-cell expressed and sereted), which is known to be the critical region for chemotaxis, were synthesized, and their anti-human immunodeficiency virus (HIV)-1 activity was examined to obtain a lead compound useful for the development of chemokine receptor-directed anti-HIV-1 drugs. A decapeptide corresponding to positions 1-10 [Ac-(10Ala-RANTES 1-10)-NH2] showed significant anti-HIV-1 activity. Ac-(10Ala, 11Ala-RANTES 5-14)-NH2 was also active, but less potent than the former. Other peptides corresponding to the positions 6-14, 7-14, and 8-14 did not show anti-HIV-1 activity. These results indicate that the sequence 1-10 of RANTES is important for the anti-HIV-1 effect.
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