Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
51 巻, 11 号
選択された号の論文の30件中1~30を表示しています
Regular Articles
  • Toshio Yajima, Shigeru Itai, Hirofumi Takeuchi, Yoshiaki Kawashima
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1223-1226
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The effects of the contents of aminoalkyl methacrylate copolymer E (AMCE) in a wax matrix on the mechanism of polymorphic transformation of glyceryl monostearate (GM) were clarified by evaluating the enthalpy change defined as 1.51 (ΔH1−ΔH2)/ΔH2, where ΔH1 and ΔH2 denote the enthalpies in the first and second thermal analyses, respectively. Using this value, K1, the rate constant of transformation from α-form to β′-form, and K2, the rate constant of transformation from β′-form to β-form, could be obtained. As the ratio of AMCE increased, K2 increased, but a minimum point existed for K1. K1 was always larger than K2, but gradually approached K2 as the ratio of AMCE increased. The optimum temperature for the transformation of GM was 50 °C, at which the enthalpy change was maximum. To prepare the wax matrix preparation of clarithromycin (CAM), we considered 40 °C the optimum treatment temperature for the transformation of GM in a CAM wax matrix compounded from CAM, GM and AMCE, since the matrices were mutually welded at above 45 °C during the spray congealing process. Although K1 and K2 were almost the same at 40 °C, the rate of transformation was accelerated by tumbling. By applying the tumbling that accelerated the transformation of GM in a CAM wax matrix, almost all of the α-form disappeared, and the release of CAM from the wax matrix diminished when the enthalpy change was more than 0.8.
  • Toshihito Hosokawa, Mari Sami, Yasuki Kato, Eiji Hayakawa
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1227-1232
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The effect of plasma components on the temperature-dependent content release property of thermosensitive liposomes has been described. Temperature-sensitive liposomes containing mitomycin C (MMC) were prepared from dipalmitoylphosphatidylcholine (DPPC liposomes) and a 7 : 3 mixture of DPPC and dipalmitoylophosphatidylglycerol (DPPC/DPPG liposomes). We defined in this study the difference in the content release between 38 °C and 44 °C as an index of the temperature-dependent content release efficiency (Δ% release). In the absence of rat plasma, the Δ% release of the DPPC liposomes and the DPPC/DPPG liposomes was 83% and 71%, respectively. However, when the release study was conducted with rat plasma, the Δ% release increased to about 96% for both liposomes. In addition, while the DPPC liposomes were destabilized by rat plasma below the gel-to-liquid crystalline phase transition temperature (Tm), MMC leakage from the DPPC/DPPG liposomes below Tm was suppressed by rat plasma. Moreover, the plasma protein binding onto lipid bilayer was concomitant with the gel-to-liquid crystalline phase transition and then enhanced the temperature-dependent release from the DPPC/DPPG liposomes. The possible mechanism of interaction between liposomes and plasma proteins, especially serum albumin, was discussed based on differential scanning calorimetry and protein binding experiments.
  • Ming-Der Wu, Ray-Ling Huang, Li-Ming Yang Kuo, Chia-Cheng Hung, Chi-Wi ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1233-1236
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The C18 dibenzocyclooctadiene lignans including three novel schizanrin F (1), G (2), H (3), along with the known kadsurarin (4), were isolated from Kadsura matsudai. A new C19 homolignan named schiarisanrin E (5), together with the known C18 lignans, gomisin B (6), G (7) and (+)-gomisin K3 (8) were obtained from Schizandra arisanensis. Gomisin B, G and (+)-gomisin K3 showed moderate to strong activity for antihepatitis in anti-HBsAg (human type B hepatitis, surface antigen) and/or anti-HBeAg (human type B hepatitis, e antigen) tests. The structural elucidations of new compounds 1—3 and 5 were based on two-dimensional (2D) NMR techniques including COSY, HMQC, HMBC, NOESY and CD spectra. Preliminary structure–activity relationship studies for these isolated lignans are also discussed.
  • Wimal Herath, Daneel Ferreira, Shabana Iqrar Khan, Ikhlas Ahmad Khan
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1237-1240
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Microbial transformation of xanthohumol using the culture broth of Cunninghamella echinulata NRRL 3655 afforded (2S)-8-[4″-hydroxy-3″-methyl-(2″-Z)-butenyl]-4′,7-dihydroxy-5-methoxyflavanone (5) and (2S)-8-[5″-hydroxy-3″-methyl-(2″-E)-butenyl]-4′,7-dihydroxy-5-methoxyflavanone (6). Xanthohumol (1) and flavanone 6 as well as (E)-2″-(2′′′-hydroxyisopropyl)-dihydrofurano[2″,3″:4′,3′]-2′,4-dihydroxy-6′-methoxychalcone (2), (2S)-2″-(2′′′-hydroxyisopropyl)-dihydrofurano[2″,3″:7,8]-4′-hydroxy-5-methoxyflavanone (3) obtained with Pichia membranifaciens showed antimalarial activity against Plasmodium falciparum.
  • Atsu Tanigake, Yohko Miyanaga, Tomoko Nakamura, Eriko Tsuji, Kenji Mat ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1241-1245
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The purpose of this study was to evaluate the ability of a quantitative prediction method using a taste sensor to determine the bitterness of clarithromycin powder suspensions of various concentrations and of a commercial clarithromycin dry syrup product (Clarith® dry syrup, Taisho Pharmaceutical Co., Ltd., Tokyo) containing aminoalkyl methacrylate polymer as a taste-masker. The bitterness of the clarithromycin dry syrup product dissolved in various beverages was also evaluated in gustatory sensation tests and using the taste sensor. In the sensor measurements, three variables were used to predict bitterness in single and multiple regression analysis: relative sensor output (R), the change of membrane potential caused by adsorption (CPA), and CPA/R ratio. The CPA values for channel 3 of the sensor predicted well the bitterness of clarithromycin powder suspensions and their filtered solutions. For Clarith® dry syrup, the sensor output was small, suggesting that aminoalkyl methacrylate polymer was successful in almost complete masking of the bitter taste of the dry syrup product. When the bitterness intensities of mixtures of 1 g of Clarith® dry syrup with 25 ml of water, coffee, tea, green tea, cocoa, milk, and a sports drink were examined, a good correlation was obtained between the results from human taste tests and the predicted values calculated on the basis of multiple regression analysis using CPA data from channel 4, and the CPA/R ratio from channel 3 of the taste sensor (r2=0.963, p<0.005). Co-administration of 1 g of Clarith® dry syrup with an acidic sports drink was found to be the most bitter using either method.
  • Akikazu Kakehi, Hiroyuki Suga, Tomonao Kako, Tsuneo Fujii, Nobuaki Tan ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1246-1252
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Some thieno[3,4-b]indolizine derivatives having a 1-naphthylmethylthio, 2-methyl-1-naphthylmethylthio, 2-naphthylmethylthio, or 9-anthrylmethylthio group at the 3-position were prepared and their intramolecular arene–arene interactions were investigated. In comparison with 3-(methylthio)thieno[3,4-b]indolizines which have no such interactions, the 1H-NMR spectra of title compounds showed large high-field shifts (δ 0.06—0.89 ppm) for the protons of the pyridine ring in the thieno[3,4-b]indolizine, and these values were considerably larger than those (δ <0.3 ppm) in 3-(benzylthio)thieno[3,4-b]indolizines. The UV spectra also exhibited a characteristic absorption band near 425 nm attributable to the arene–arene interaction. In the X-ray analyses of some compounds, however, the presence of both the gauche and the anti conformers at the sulfide spacer were confirmed.
  • Juziro Nishijo, Shiho Moriyama, Sachiko Shiota
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1253-1257
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The interaction of cholesterol with several cyclodextrins (CDs) was investigated in water using solubility method. It was found that heptakis (2,6-di-O-methyl)-β-CD (DOM-β-CD) forms two types of soluble complex, with molar ratios of 1 : 1 and 1 : 2 (cholesterol : DOM-β-CD), and neither a soluble nor insoluble complex is formed between cholesterol and α-CD, β-CD, and γ-CD, although a minor soluble complex formation was observed between cholesterol and 2-hydroxylpropyl-β-CD. The thermodynamic parameters for 1 : 1 and 1 : 2 complex formation of cholesterol with DOM-β-CD obtained from the changes in K with temperature are as follows: ΔG°1 : 1=−11.6 kJ/mol at 25 °C (K1 : 1=1.09×102 M−1); ΔH°1 : 1=−3.38 kJ/mol; TΔS°1 : 1=8.25 kJ/mol; ΔG°1 : 2=−27.1 kJ/mol at 25 °C (K1 : 2=5.68×104 M−1); ΔH°1 : 2=−3.96 kJ/mol; and TΔS°1 : 2=23.2 kJ/mol. The formation of the 1 : 2 complex occurred much more easily than that of the 1 : 1 complex. The driving force for 1 : 1 and 1 : 2 complex formation was considered to be mainly hydrophobic interaction. Also, based on the measurements of proton nuclear magnetic resonance spectra and studies with Corey–Pauling–Koltun atomic models, the probable structutures of the 1 : 2 complex were estimated.
  • Yasuko In, Shouitirou Kishima, Katsuhiko Minoura, Takeru Nose, Yasuyuk ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1258-1263
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    X-Ray crystal structures of four different fluorine-substituted phenylalanines (two mono- and two tri-substitutions) were analyzed to investigate the effect of fluorine atom on the association pattern of benzene rings. Although respective structures showed similar molecular packing in such a way that the layers of hydrophobic benzene rings and hydrophilic amino/carboxyl groups were alternately running along a crystallographic axis, the association patterns of benzene rings were different depending on the substitution position and number of fluorine atoms. The general features could be that the partially displaced face-to-face interactions are increased with increase in the number of fluorine atoms, whereas the edge-to-face interactions are decreased. The C–H bond next to a fluorine-substituted carbon atom could serve as a donor of an intermolecular C–H···F hydrogen bond.
  • Ling-Yun Ma, Shuang-Cheng Ma, Feng Wei, Rui-Chao Lin, Paul Pui-Hay But ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1264-1267
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Five compounds have been isolated from the dried whole plants of Selaginella uncinata, two of them were new chromone glycosides, 5-hydroxy-2,6,8-trimethylchromone 7-O-β-D-glucopyranoside (uncinoside A) and 5-acetoxyl-2,6,8-trimethylchromone 7-O-β-D-glucopyranoside (uncinoside B). Their structures were elucidated by spectroscopic methods including one- and two-dimensional NMR techniques. The other three compounds were identified as 8-methyl eugenitol, amentoflavone and hinokiflavone. Uncinoside A and B showed potent antiviral activities against respiratory syncytial virus (RSV) with IC50 value of 6.9 and 1.3 μg/ml, moderate antiviral activities against parainfluenza type 3 virus (PIV 3) with IC50 value of 13.8 and 20.8 μg/ml, respectively.
  • Kunihiko Mohri, Yuhya Watanabe, Yuki Yoshida, Mitsuru Satoh, Kimiaki I ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1268-1272
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Condensation of glycosylated arylaldehyde with acetylacetone–B2O3 complex gave a corresponding diglycosylcurcuminoid, and a similar reaction using a mixture of arylaldehyde and glycosylarylaldehyde gave an unsymmetrical monoglycosylcurcuminoid, both as boron-complexes. The boron was removed from the complexes by heating in methanol, thus achieving the synthesis of di- and mono-glycosylcurcuminoids.
  • Hiroki Kakuta, Aya Tanatani, Kazuo Nagasawa, Yuichi Hashimoto
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1273-1282
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Potent, specific, chemically stable and non-peptide/small-molecular inhibitors of puromycin-sensitive aminopeptidase, such as 3-(2,6-diethylphenyl)-2,4(1H,3H)-quinazolinedione (PAQ-22, 5), were prepared by the structural development of a potent PSA inhibitor, 2-(2,6-diethylphenyl)-1,2,3,4-tetrahydroisoquinoline-1,3-dione (PIQ-22, 4). The design was carried out partly by applying electrostatic potential field information obtained from PIQ-22 (4) and its derivatives based on thalidomide (2). This information revealed that a positive electrostatic potential field around the benzylic methylene in the tetrahydroisoquinoline ring is necessary for potent activity. Lineweaver–Burk plot analysis showed that PAQ-22 (5) and its derivatives inhibit puromycin-sensitive aminopeptidase (PSA) in a non-competitive manner. These potent and specific PSA inhibitors showed dose-dependent cell invasion-inhibitory activity in a Matrigel assay using mouse melanoma B16F10/L5 cells, in spite of their low cell toxicity.
  • Shuji Yasuike, Tsutomu Kiharada, Takashi Tsuchiya, Jyoji Kurita
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1283-1288
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    The C-unsubstituted 3-benzoheteroepines (2a—g) containing group 15 (P, As, Sb, and Bi) and group 16 (S, Se, and Te) heavier elements were prepared by the reaction of the corresponding metal reagents with (Z,Z)-o-bis(β-lithiovinyl)benzene (5) which was derived in two steps from a common o-phthalaldehyde (3). The heteroepines (2) thus obtained were thermally labile towards heteroatom extrusion, and their half-lives on heating estimated from 1H-NMR spectral analysis showed that the 3-benzoheteroepines (2) were far less stable than the corresponding 1-benzoheteroepines (1). The 2,4-bis(trimethylsilyl)-3-benzoheteroepines (17) containing Sb, Bi, and Te were also prepared from o-diiodobenzene (9) in 6 steps and were found to be more stable than the corresponding C-unsubstituted heteroepines (2).
  • Sumie Yoshioka, Yukio Aso, Shigeo Kojima
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1289-1292
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Laboratory- and rotating- frame spin-lattice relaxation times (T1 and T) of 1H and 13C in lyophilized poly(vinylpyrrolidone) (PVP) and methylcellulose (MC) are determined to examine feasibility of using T1 and T as a measure of molecular motions on large time scales related to the storage stability of lyophilized formulations. The T of proton and carbon was found to reflect the mobility of PVP and MC backbones, indicating that it is useful as a measure of large-time-scale molecular motions. In contrast to the T, the T1 of proton measured in the same temperature range reflected the mobility of PVP and MC side chains. The T1 of proton may be useful as a measure of local molecular motions on a smaller-time-scale, although the measurement is interfered by moisture under some conditions. The temperature dependence of T1 and T indicated that methylene in the MC molecule had much higher mobility than that in the dextran molecule, also indicated that methylene in the PVP side chain had a higher mobility than that in the MC side chain.
  • Takashi Nakamura, Takayuki Motoyama, Takatsugu Hirokawa, Shuichi Hiron ...
    原稿種別: Regular Article
    専門分野: [not specified]
    2003 年 51 巻 11 号 p. 1293-1298
    発行日: 2003年
    公開日: 2003/11/01
    ジャーナル フリー
    Homology modeling was used to construct a model of the three-dimensional structure of pentachlorophenol 4-monooxygenase (PcpB). A PSI-BLAST homology search was initially performed to identify the 3D structure of proteins homologous with PcpB. The feasibility of modeled structures of PcpB was evaluated by Verify3D, which calculated structural compatibility scores based on 3D–1D profiles. The predicted structure of PcpB had an acceptable 3D–1D self-compatibility score, beyond the incorrect fold score threshold. A PcpB–pentachlorophenol (PCP) complex was then constructed utilizing the modeled PcpB structure. After energy minimization of the complex, and successive minimizations of the system that consisted of the complex and the water layer surrounding the complex, the molecular dynamics of the system were simulated. The active-site residues of PcpB were identified on the basis of the modeled structure, and PcpB mutants were then designed to change the active site residues, expressed, and purified by affinity chromatography. The mutant activity was compared with that of the wild-type to investigate the validity of the modeled structure. The experimental results suggested that Phe85, Tyr216, and Arg235 were relevant to enzyme activity, and that Tyr397 and Phe87 were important for stabilization of the structure of PcpB.
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