Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
54 巻, 9 号
選択された号の論文の27件中1~27を表示しています
Regular Articles
  • Muhammad Shaiq Ali, Waqar Ahmed, Andrea Florence Armstrong, Syed Amir ...
    2006 年 54 巻 9 号 p. 1235-1238
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    A new sesquiterpene-lactone (nubenolide) belonging to the guaianolide class along with its acetate (nubenolide acetate) and a dimer (bisnubenolide) have been isolated from Salvia nubicola collected from Quetta, Pakistan. Structures of all three new metabolites were elucidated with the aid of spectroscopic techniques including 2D-NMR. However, the structure of nubenolide was finally confirmed via single-crystal X-ray diffraction method.
  • Hedong Bian, Mei Li, Qing Yu, Zhenfeng Chen, Jianniao Tian, Hong Liang
    2006 年 54 巻 9 号 p. 1239-1243
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    This study examined the interaction of indirubin with bovine serum albumin (BSA) at three temperatures (286, 297, 308 K) at pH 7.40. In the presence of indirubin, the drug–BSA binding mode, binding constant and the protein structure changes in aqueous solution were determined by fluorescence quenching methods including Fourier transform infrared (FT-IR) spectroscopy and UV–Vis spectroscopy. The FT-IR change indicates that indirubin binds to BSA. The change in protein secondary structure accompanying ligand binding has been proved by fluorescence spectra data. The thermodynamic parameters, the enthalpy change (ΔH), and the entropy change (ΔS) calculated by the van't Hoff equation possess small negative (−2.744 kJ·mol−1) and positive values (112.756 J·mol−1·K−1), respectively, which indicated that hydrophobic interactions play the main role in the binding of indirubin to BSA. Furthermore, the displacement experiment shows that indirubin can bind to the subdomain IIA and the distance between the tryptophan residues in BSA and indirubin bound to site I was estimated to be 2.24 nm according to Föster's equation on the basis of fluorescence energy transfer.
  • Yoshito Ohnishi, Satoru Watano
    2006 年 54 巻 9 号 p. 1244-1247
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Wet granulation is a very important process and a reliable evaluation method for formulation study; thus it requires appropriate process control. In this study, a novel and effective method that involves a compression test of wet powder is proposed. Here, the compression energy, which could predict the capability of the wet powder for extrusion granulation as well as the physical properties of the final products, is used as a novel characteristic of wet powder. The compression energy was defined as the energy consumption derived from the compression speed and the transmission loss during the compression test. Lactose monohydrate was mixed with various additives such as hydroxypropylcellulose in the mass ratio of 0—10%. Various amounts of water were fed into the mixtures, which were kneaded in a planetary motion mixer to prepare the kneaded wet powders. The characteristics of these powders were evaluated by the compression energy. The kneaded wet powders were then extruded through an extrusion granulator, the electrical loads of the granulator during the operation were analyzed as the extrusion energy, and the physical properties of extruded granules were investigated. As a result, the granule strength and granule size distribution showed a good correlation with the compression energy. A good correlation was also observed between the compression energy of the kneaded wet powder and the extrusion energy regardless of the different additives and water contents. It was concluded that the compression energy of the wet powder could be used for the formulation study and the process control of wet granulation.
  • Lei Ji, Fen-Er Chen, Xiao-Qing Feng, Erik De Clercq, Jan Balzarini, Ch ...
    2006 年 54 巻 9 号 p. 1248-1253
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    A series of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) analogues bearing a 6-(1-naphthoyl) group of non-nucleoside human immunodeficiency virus (HIV) reverse transcriptase inhibitors were synthesized and evaluated for their activity against HIV-1 and HIV-2. It was found that most of these compounds showed good activity against HIV-1. Among them, compound 5-isopropyl-6-(1-naphthoyl)-1-[(2E)-3-phenylallyl]-2,4-pyrimidinedione (23) displayed the greatest inhibitory potency (IC50=0.14 μM), which is about 35-fold more active than HEPT and DDI. To rationalize the relationships between structure and activity of these novel compounds, a three-dimensional quantitative structure–activity relationship (3D-QSAR) model was also generated. The results provided a tool for guiding the further design of more potent antiviral agents and for predicting the affinity of related compounds.
  • Rongqin Huang, Wuli Yang, Chen Jiang, Yuanying Pei
    2006 年 54 巻 9 号 p. 1254-1258
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Our aim is to test the characteristics and expression activity in brain capillary endothelial cells (BCECs) of DNA-loaded nanoparticles before and after the modification with Antennapedia peptide (Antp). Chitosan (CH), polyethylenimine (PEI) and polyamidoamine (PAMAM) were chosen to prepare the nanoparticles; Lipofectamine 2000 served as control. The incorporation efficiency was determined by agarose gel electrophoresis and PicoGreen assay. Transmission electron microscopy was performed to observe the diameter. The expression efficiency was qualified with fluorescence microscopy and quantified with the luciferase assay system. Heparin and DNase I were employed to investigate the stability. The results indicated that the gene products of DNA/CH nanoparticles and DNA/Lipofectamine 2000 complexes whether modified or unmodified with Antp could not be observed within BCECs. The DNA/PEI nanoparticles and DNA/PAMAM nanoparticles could be internalized into BCECs to a certain extent, and the expression efficiency was enhanced significantly with the modification of Antp. The diameter increased from 100 to 200 nm after modification with Antp. The nanoparticles could protect themselves from the displacement of anionic substances and the digestion of DNase I. These observations demonstrated that Antp, polymer and DNA could form stable nanoparticles, and the modification of Antp can enhance the expression efficiency of DNA-loaded nanoparticles in BCECs.
  • Lina Du, Junping Cheng, Qiang Chi, Jiankun Qie, Yan Liu, Xingguo Mei
    2006 年 54 巻 9 号 p. 1259-1265
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    A sustained release poly(DL-lactide-co-glycolide) (PLGA) microsphere delivery system to treat prostate cancer for a luteinizing hormone-releasing hormone (LHRH) antagonists, LXT-101 was prepared and evaluated in the paper. LXT-101 microspheres were prepared from PLGA by three methods: (1) double-emulsion solvent extraction/evaporation technique, (2) single-emulsion solvent extraction/evaporation technique, and (3) S/O/O (solid-in-oil-in-oil) method. The microspheres were investigated on drug loading, particle size, surface morphology and in vitro release profiles. An accelerated release approach was also established in order to expedite the evaluation periods. The in vivo evaluation of the microspheres was made by monitoring testosterone levels after subcutaneous administration to rats. The LXT-101 PLGA microspheres showed smooth and round surfaces according to a scanning electron microscopic investigation, and average particle size of ca. 30 μm according to laser diffractometry. The drug encapsulation efficiency of microspheres was influenced by LA/GA ratio of PLGA, salt concentrations, solvent mixture and preparation methods. Moreover, LA/GA ratio of PLGA, different preparation methods and different peptide stabilizers affected in vitro release of drugs. In vivo study, the testosterone levels were suppressed to castration up to 42 d as for the 7.5 mg/kg dose. And in vivo performance of LXT-101 microspheres was dose-dependent. The weights of rat sexual organs decreased and histopathological appearance of testes had little changes after 4-month microspheres therapy. This also testified that LXT-101 sustained release microspheres could exert the efficacy to suppress the testosterone level to castration with little toxicity. In conclusion, the PLGA microspheres could be a well sustained release system for LXT-101.
  • Kyung-Hee Park, Jae-Rin Lee, Hwa-Sun Hahn, Young-Hoon Kim, Chang-Dae B ...
    2006 年 54 巻 9 号 p. 1266-1270
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Tyrosinase requires two copper ions at the active site, in order to oxidize phenols to catechols. In this study, the inhibitory effect of the copper-chelating compound, ammonium tetrathiotungstate (ATTT), on the tyrosinase activity was investigated. ATTT was determined to inactivate the activity of mushroom tyrosinase, in a dose-dependent manner. The kinetic substrate reaction revealed that ATTT functions as a kinetically competitive inhibitor in vitro, and that the enzyme–ATTT complex subsequently undergoes a reversible conformational change, resulting in the inactivation of tyrosinase. In human melanin-producing cells, ATTT evidenced a more profound tyrosinase-inhibitory effect than has been seen in the previously identified tyrosinase inhibitors, including kojic acid and hydroquinone. Our results may provide useful information for the development of whitening agent.
  • Qing He, Zhi-Wei Ge, Yue Song, Yi-Yu Cheng
    2006 年 54 巻 9 号 p. 1271-1275
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    An high performance liquid chromatography (HPLC) coupled with diode array detector (DAD) and electrospray ionization tandem mass spectrometry (ESI/MSn) method was developed for quality evaluation of Cortex Moutan through identification of common constituents based on chromatographic fingerprints and determination of key pharmacological compounds. The representative chromatographic fingerprints of Cortex Moutan were obtained by analyzing 10 batches of samples under the optimized HPLC conditions and the results showed that the chromatographic profiles of the analyzed samples were very similar. Total of nineteen common peaks were detected and seventeen of them were identified rapidly by their characteristic UV profile and the information of molecular structure provided by ESI/MSn experiments. Simultaneously, five key pharmacological compounds, namely gallic acid, oxypaeoniflorin, paeoniflorin, benzoylpaeoniflorin and paeonol, were determined by the validated HPLC-DAD method. The linear calibration curves were acquired with correlation coefficients higher than 0.999. The precisions of intra-day and inter-day were not exceeding 3.1%, and the recoveries of five analytes were from 92.86 to 99.35%. This developed method that combined the chromatographic fingerprints and quantification assay ensured the phytoequivalence and pharmacological effects of Cortex Moutan and was successfully applied to the quality control of Cortex Moutan.
  • Saburo Murata, Hideki Ito, Takashi Izumi, Akinori Chikushi
    2006 年 54 巻 9 号 p. 1276-1280
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Stmerin® D, a pressurized metered dose inhaler (MDI) for treatment of asthma, contains CFCs (chlorofluorocarbons) as a propellant. For the CFC replacement study, two formulations were prepared using hydrofluoroalkanes (HFA-134a and HFA-227) and the effect of storage on the spray performance was investigated under accelerated stress conditions. Drug stability, moisture content and spray performances such as the emitted dose uniformity and aerodynamic particle size distribution were evaluated. Drug content did not change after 3 months storage at 40 °C/75% RH. However, the emitted dose uniformity varied and the respirable fraction (RF) was reduced remarkably. While stored at 40 °C/ambient for 3 months, no change was observed in either drug content or spray performances. This study clarified that the moisture content in the canister played an important role on the spray performance, and it changed not only the emitted dose uniformity but also the particle size distribution. Consequently, in order to improve the stability of the spray performance of aerosol prepared with HFAs, moisture permeation into the canister must be controlled.
  • Noriyasu Hada, Yuhua Jin, Tadahiro Takeda, Isao Ohtsuka, Shoko Yokoyam ...
    2006 年 54 巻 9 号 p. 1281-1284
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    6-N-[2-(Tetradecyl)hexadecanamido]hexyl β-D-glucopyranosyluronic acid-(1→6)-β-D-galactopyranosyl-(1→6)-β-D-galactopyranoside (1) and its clustering compound (2) carrying a tetravalent sugar unit, which are new model compounds related to a major antigenic epitope from antiulcer pectic polysaccharide of Bupleurum falcatum L., were synthesized and the distributions of 1 and 2 in mixed ganglioside (GM1, GD1a or GT1b)/phospholipid (DPPC) monolayers were observed using atomic force microscopy (AFM). AFM images showed that 1 was distributed in the GM1, GD1a and GT1b region of the mixed monolayers, in which 1 was miscible with GD1a. Specific distribution of 1 was observed in the mixed GM1/DPPC monolayer. Compound 2 was miscible with GM1, while 2 formed associations with GD1a and GT1b in the mixed monolayers. The distribution mode of 1 and 2 was different among the mixed ganglioside/DPPC monolayers.
  • Wen-Wei Fu, Noriko Shimizu, Tadahiro Takeda, De-Qiang Dou, Baohui Chen ...
    2006 年 54 巻 9 号 p. 1285-1287
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Three new A-ring lactone triterpenoid saponins, platycoside M-1 [3-O-β-D-glucopyranosyl platycogenic acid A lactone], platycoside M-2 [3-O-β-D-glucopyranosyl platycogenic acid A lactone 28-O-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside], and platycoside M-3 [3-O-β-D-glucopyranosyl platycogenic acid A lactone 28-O-β-D-xylopyranosyl-(1→4)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranoside], were isolated from the roots of Platycodon grandiflorum A. DC. Their chemical structures were elucidated on the basis of their spectral data and chemical evidence.
  • Emi Tokuyama, Takeshi Shibasaki, Hideo Kawabe, Junji Mukai, Sachie Oka ...
    2006 年 54 巻 9 号 p. 1288-1292
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    The purpose of the present study was to evaluate the bitterness-suppressing effect of L-ornithine (L-Orn) on single or mixed solutions of branched-chain amino acids (BCAAs) using human gustatory sensation tests and an artificial taste sensor. The BCAAs tested (L-isoleucine (L-Ile), L-leucine (L-Leu), and L-valine (L-Val)) are the main components of various enteral nutrients or supplements. The bitterness-suppression effect of L-Orn was also compared with the effect of L-Arg. L-Orn was effective in suppressing the bitterness of single or mixed solutions of BCAAs in human gustatory sensation tests, the effect being similar to or greater than that of L-Arg. The artificial taste sensor was able to predict the bitterness-suppressing effects of L-Orn and L-Arg. The response electric potential patterns of L-Val, L-Leu and L-Ile solutions to which 100 mM L-Arg had been added were quite similar to the sensor response patterns of the 100 mM L-Arg solutions alone. The relative response electric potential patterns of L-Val, L-Leu or L-Ile solutions containing 100 mM L-Orn in channels 5—8 (positively charged) are similar to that of single solution of 100 mM L-Orn.
  • Fumiaki Kisa, Koji Yamada, Tomofumi Miyamoto, Masanori Inagaki, Ryuich ...
    2006 年 54 巻 9 号 p. 1293-1298
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Three new disialo- and trisialo-gangliosides, CEG-6 (6), CEG-8 (8), and CEG-9 (9), were obtained, together with one known ganglioside, HLG-3 (7), from the lipid fraction of the chloroform/methanol extract of the sea cucumber Cucumaria echinata. The structures of the new gangliosides were determined on the basis of chemical and spectroscopic evidence to be 1-O-[α-L-fucopyranosyl-(1→11)-(N-glycolyl-α-D-neuraminosyl)-(2→4)-(N-acetyl-α-D-neuraminosyl)-(2→6)-β-D-glucopyranosyl]-ceramide (6) and 1-O-[(N-glycolyl-D-neuraminosyl)-(2→11)-(N-glycolyl-D-neuraminosyl)-(2→4)-(N-acetyl-D-neuraminosyl)-(2→6)-D-glucopyranosyl]-ceramide (8, 9). The ceramide moieties of each compound were composed of an homogeneous sphingosine or phytosphingosine base and heterogeneous 2-hydroxy or nonhydroxylated fatty acid units. These gangliosides showed neuritogenic activity toward the rat pheochromocytoma cell line PC-12 in the presence of nerve growth factor.
  • Maiko Hayashida, Miyuki Ishizaki, Hiroshi Hara
    2006 年 54 巻 9 号 p. 1299-1303
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    Selective mono-deallylation of O,O′-diallylcatechols using 10% Pd/C was investigated to give the correspond-ing allylphenols. A similar reaction of 3-methylene-1,5-benzodioxepanes afforded O-methacryl catecohols. When substrates bearing various substituents on the benzene ring were subjected to the reaction, regioselective cleavage of an ether bond occurred at the side of para position to an electron-withdrawing group on the aromatic ring. On the other hand, an electron-donating group did not cause any selectivity.
  • Bunpei Hatano, Daisuke Kubo, Hideyuki Tagaya
    2006 年 54 巻 9 号 p. 1304-1307
    発行日: 2006年
    公開日: 2006/09/01
    ジャーナル フリー
    We found that diarylmethanols and diaryl ketones were smoothly reduced to the corresponding diarylalkanes using supercritical 2-propanol in good yields. Furthermore, we determined the specific reaction of fluorene using supercritical methanol at high temperature.
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