Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
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Volume 57, Issue 12
Displaying 1-23 of 23 articles from this issue
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Review
  • Structural Studies of Specific Intermolecular Interactions and Self-Aggregation of Biomolecules and Their Application to Drug Design
    Toshimasa Ishida
    Article type: Review
    2009 Volume 57 Issue 12 Pages 1309-1334
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1309
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    Information on the structural basis of intermolecular recognition or self-aggregation of biomolecules at the atomic level is important to understand biological functions and to develop devices for treating disorders caused by abnormal functions. Thus structural analysis of specific intermolecular or intramolecular interactions of biomolecules has been performed using various physicochemical approaches. Herein, the following three subjects are reviewed: (1) structural analyses of mRNA cap structure recognition by eukaryotic initiation factor 4E and its functional regulation by endogenous 4E-binding protein; (2) structural studies of self-aggregation mechanism of microtubule-binding domain in tau protein and aggregation inhibitor; and (3) molecular design of cathepsin B-specific inhibitor.
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Regular Articles
  • FAMSD: A Powerful Protein Modeling Platform that Combines Alignment Methods, Homology Modeling, 3D Structure Quality Estimation and Molecular Dynamics
    Kazuhiko Kanou, Mitsuo Iwadate, Tomoko Hirata, Genki Terashi, Hideaki ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1335-1342
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1335
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    The prediction of a protein three-dimensional (3D) structure is one of the most important challenges in computational structural biology. We have developed an automatic protein 3D structure prediction method called FAMSD. FAMSD is based on a comparative modeling method which consists of the following four steps: (1) generating and selecting sequence alignments between target and template proteins; (2) constructing 3D structure models based on each selected alignment; (3) selecting the best 3D structure model and (4) refining the selected model. In the FAMSD method, sequence alignment programs such as a series of BLAST programs, SP3 and SPARKS2 programs, the homology modeling program FAMS (Full Automatic Modeling System), the model quality estimation program CIRCLE and the molecular dynamics program APRICOT were used in combination to construct high quality protein models. To assess the FAMSD method we have participated in the 8th Critical Assessment of Techniques for Protein Structure Prediction (CASP8) experiment. The results of our original assessment indicate that the FAMSD method offers excellent capability in packing side-chains with the correct torsion angles while avoiding the formation of atom–atom collisions. Since side-chain packing plays a significant role in defining the biological function of proteins, this method is a valuable resource in biological, pharmaceutical and medicinal research efforts.
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  • Effect of Pharmaceutical Excipients on the Stability of Trichlormethiazide Tablets under Humid Conditions
    Reiko Teraoka, Yuki Matsushima, Isao Sugimoto, Kana Inoue, Shin-ya Mor ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1343-1347
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1343
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    The stability of trichlormethiazide (TCM) and the drug in the nine products available on the market (the original tablet (B) and 8 generic tablets (G1—G8)) were investigated under humid conditions. TCM was non-hygroscopic and was not degraded under humid conditions. Drug degradation in aqueous ethanol was accelerated with increased water concentration, and the drug stability in buffer solution was improved with decreased pH. TCM decomposition was not detected in each unwrapped tablet at low relative humidity. However, rapid degradation was observed for products G1 and G2, while product B and G7 showed higher stability at high relative humidity. The stability of products G1 and G2 decreased with increasing humidity. The same results were observed for the tablets in press-through packages (PTP), but the degradation rate was much slower than tablets without PTP packages. These results suggested that the adsorbed moisture by excipients cause TCM degradation. Various pharmaceutical excipients are added to TCM tablets and these vary between different pharmaceutical companies. Intact drug and pharmaceutical excipients, including lactose, microcrystalline cellulose, corn starch, hydroxypropylcellulose (HPC), low substituted HPC (L-HPC), calcium stearate, and light anhydrous silicic acid, were mixed, and the sample mixtures were stored in humid conditions. It was found that the TCM content decreased significantly in a binary mixture of TCM/HPC 1 : 1.
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  • Synthesis of New 2-Naphthyl Ethers and Their Protective Activities against DNA Damage Induced by Bleomycin–Iron
    Bakr F. Abdel-Wahab, Abdel-Aziz S. El-Ahl, Farid A. Badria
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1348-1351
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1348
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    The reaction of 2-naphthaloxyacetic acid with thiosemicarbazide in the presence of phosphoryl chloride, followed by treatment with phenacylbromides, led to the formation of imidazo[2,1-b][1,3,4]thiadiazoles 3a—c. 2-(Naphthalen-3-yloxy)acetohydrazide 4 on treatment with ethyl 2-(2-arylhydrazono)-3-oxobutanoates (5a—c), 2-methoxymethylene)malononitrile, or ethyl 2-cyano-3,3-bis(methylthio)acrylate led to the formation of substituted pyrazoles 6—8. The reaction of the hydrazide 4 with hydrazonoyl chlorides 9a—c and 1,2,4,5-benzene tetracarboxylic-1,2:4,5-dianhydride produced bis-diazo compounds 10a—c and dimide 11 respectively. All new compounds were tested for their protective activity against DNA damage induced by bleomycin–iron complex. Compound 2 showed the greatest protection against DNA damage, thus diminishing chromogen formation between the damaged DNA and thiobarbituric acid.
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  • Galloyl and Hexahydroxydiphenoyl Esters of Phenylpropanoid Glucosides, Phenylpropanoids and Phenylpropanoid Glucosides from Rhizome of Balanophora fungosa
    Natcha Panthama, Somdej Kanokmedhakul, Kwanjai Kanokmedhakul
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1352-1355
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1352
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    Five new galloyl and (S)-hexahydroxydiphenyl (HHDP) esters of phenylpropanoid glucosides; 1-O-(E)-coumaroyl-3-galloyl-4,6-(S)-HHDP-β-D-glucopyranose (21), 1-O-(E)-coumaroyl-3,4,6-trigalloyl-β-D-glucopyranose (22), 1-O-(E)-caffeoyl-3,4,6-trigalloyl-β-D-glucopyranose (23), 1-O-(E)-cinnamoyl-3-galloyl-4,6-(S)-HHDP-β-D-glucopyranose (24), and 1-O-(E)-cinnamoyl-4-galloyl-β-D-glucopyranose (25), together with twenty known compounds which were identified as four triterpenes (1, 2, 3, 5), one steroid (4), one lignan (6), three phenylpropanoids (7, 8, 14), five phenylpropanoid glucosides (10, 12, 13, 15, 16), five galloyl and HHDP esters of phenylpropanoid glucosides (11, 17—20), and one bischroman (9). Their structures were determined on the basis of 1D and 2D spectroscopic data.
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  • Thermal Treating of Acrylic Matrices as a Tool for Controlling Drug Release
    Davood Hasanzadeh, Solmaz Ghaffari, Farnaz Monajjemzadeh, MHD-Kamal Al ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1356-1362
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1356
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    The purpose of the present study was to investigate the effect of thermal-treating on the release of ibuprofen from the granules prepared using aqueous dispersions of Eudragit. To accomplish this goal, different formulations were prepared using wet granulation method containing two different types of Eudragit aqueous dispersions, RS30D, RL30D and Avicel as filler. Tablets were prepared using direct compression method. The prepared tablets were thermally treated at 50 and 70 °C for 24 h. The drug release from tablets was assessed before and after thermal-treating. The results of release study showed that, thermally-treating the tablets at the temperatures higher than glass transition temperature (Tg) of the polymer can decrease the drug release from matrices. For mechanistic evaluation of the effect of thermal-treating, powder X-ray diffraction (XPD), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), Fourier transform infrared (FT-IR) and helium pycnometer have been employed. The SEM graphs showed that the tablets have smoother surface with less porosity after thermal-treating. FT-IR spectra showed no change in the spectrum of thermally-treated tablet compared to control. In DSC graphs, no crystalline change was seen in the heat-treated samples of ibuprofen tablets, but decreased and widened peak size were related to the probable formation of solid solution of ibuprofen in Eudragit matrix. The results of helium pycnometer showed a significant decrease in the total porosity of some heat-treated samples. This study revealed the importance of thermal treating on the drug release from sustained release tablets containing Eudragit polymer.
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  • Effect of Caffeine Complexation on the Photolysis of Riboflavin in Aqueous Solution: A Kinetic Study
    Iqbal Ahmad, Sofia Ahmed, Muhammad Ali Sheraz, Muhammad Aminuddin, Fai ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1363-1370
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1363
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    The effect of caffeine complexation with riboflavin on the kinetics of riboflavin photolysis in the pH range 2.0—10.5 has been studied. The photolysis of riboflavin solutions (5×10−5 M) was carried out in the presence of caffeine (0.5—2.5×10−4 M) using a visible radiation source. A specific multicomponent spectrophotometric method was used for the determination of riboflavin and photoproducts in photolysed solutions. The apparent first-order rate constants (k) for the photolysis reactions range from 2.71×10−4 to 4.26×10−2 min−1. The values of the rate constants decrease with increasing concentrations of caffeine indicating its inhibitory effect on the reactions. The second-order rate constants (k′) for the caffeine inhibited reactions lie in the range of 0.13 to 5.10×10−3 M−1 min−1. The log k–pH profiles for the photolysis reactions at various caffeine concentrations involve multiple steps indicating a gradual increase in the rate up to pH 10. The lower rates at pH 2.0 and 10.5 are due to the ionization of riboflavin as evident from fluorescence measurements. The k′–pH profile for the interaction of riboflavin with caffeine represents a bell-shaped curve in the pH range 3—6 followed by a sigmoid curve in the pH range 7—10. The inhibition of photolysis of riboflavin in the presence of caffeine is a result of the monomeric interaction and complex formation of caffeine with riboflavin. The photochemical interaction of riboflavin with caffeine suggests that a pH around 6 is most appropriate for the stabilization of the vitamin. At this pH the complex shows the highest stability constant.
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  • Tetraazaindenes Derived from Dihydropyrazines with DNA Strand-Breaking Activity
    Kazuhide Nakahara, Shinji Takechi, Koki Yamaguchi, Kazunobu Harano, Ta ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1371-1375
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1371
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    Dihydropyrazines (DHPs), which exhibit DNA strand-breaking activity and other biological activities associated with the generation of radical species, reacted with thiourea to give tetraazaindene (TAI) derivatives, despite thiourea is a well known radical scavenger. The structural determination of the TAIs was carried out and formation mechanism of TAI was investigated.
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  • Synthesis, Antimicrobial and Antioxidant Activities of Sulfone Linked Bis Heterocycles—Pyrazolyl Oxadiazoles and Pyrazolyl Thiadiazole
    Venkatapuram Padmavathi, Sanapalli Nagi Reddy, Konda Mahesh
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1376-1380
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1376
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    A new class of bis heterocycles—sulfone linked pyrazolyl oxadiazoles and thiadiazoles were developed from Z-styrylsulfonylacetic acid. The pyrazolyl thiadiazoles exhibited excellent antimicrobial activity whereas pyrazolyl oxadiazoles displayed good antioxidant activity.
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  • Serratene Triterpenoids from Palhinhaea cernua var. sikkimensis
    Jian Yan, Lirong Sun, Xianming Zhang, Zhongrong Li, Lin Zhou, Minghua ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1381-1384
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1381
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    Seven new serratene triterpenoids, 3α,21β,29-trihydroxy-16-oxoserrat-14-en-24-oic acid (1), 3β,21β,29-trihydroxy-16-oxoserrat-14-en-24-oic acid (2), 3β,21β,29-trihydroxyserrat-14-en-24-oic acid 3β-(4-hydroxybenzoate) (3), 3β,21β,29-trihydroxyserrat-14-en-24-oic acid 3β-(4-hydroxy-3-methoxybenzoate) (4), 3β,14α,15α,21β,29-pentahydroxyserrat-14-en-24-oic acid 3β-(4-hydroxybenzoate) (5), 3α,21β,24,29-tetrahydroxyserrat-14-en-16-one (6), 3α,21β,30-trihydroxyserrat-14-en-16-one (7) were isolated from Palhinhaea cernua var. sikkimensis, together with twelve known compounds (8—19). Their chemical structures were elucidated on the basis of spectroscopic evidence and comparison with literature values.
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  • Preparation of New Nitrogen-Bridged Heterocycles 67. Syntheses of α,α′-Bis[(thieno[3,4-b]indolizin-3-yl)thio]-o-, m-, and p-xylene Derivatives and Their Conformational Structures
    Akikazu Kakehi, Hiroyuki Suga, Yukihisa Okumura, Masatoshi Shinohara, ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1385-1390
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1385
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    The alkaline treatment and dehydrogenation of pyridinium salts, formed from the S-alkylations of 3-(1-pyridinio)thiophene-2-thiolates with α,α-dibromo-o-, m-, or p-xylene, provided the corresponding α,α′-bis[(thieno[3,4-b]indolizin-3-yl)thio]-o-, m-, and p-xylene derivatives in low to good yields. Both 1H-NMR and UV–Vis spectra of these products supported distinctly the predominance of the gauche–gauche conformation in relation to the two sulfide linkages as the spacer in these molecules. On the other hand, the X-ray analyses indicated the expected gauche–gauche conformation for the m- and the p-xylene derivatives, but the anti–anti one for the o-xylene derivative.
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  • One-Step Synthesis and Bioassay of N-Phosphoramidophosphonates
    Mudumala Veera Narayana Reddy, Avula Balakrishna, Mungara Anil Kumar, ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1391-1395
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1391
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    A simple one-step synthesis was accomplished for the preparation of N-phosphoramidophosphonates by a direct reaction of phosphoramidate (1) with heterocyclic aldehydes (2a—j) and dialkyl phosphites at 60—70 °C in the presence of tetramethylguanidine. The tetramethylguanidine not only catalyses this reaction but also helps to form pure products in high yields in lesser time. They exhibited good insecticidal and antioxidant properties.
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  • Time-Dependent Changes of Oxytocin Using 1H-NMR Coupled with Multivariate Analysis: a New Approach for Quality Evaluation of Protein/Peptide Biologic Drugs
    Akiko Ohno, Nana Kawasaki, Kiyoshi Fukuhara, Haruhiro Okuda, Teruhide ...
    Article type: Regular Article
    2009 Volume 57 Issue 12 Pages 1396-1399
    Published: December 01, 2009
    Released on J-STAGE: December 01, 2009
    DOIhttps://doi.org/10.1248/cpb.57.1396
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    A new method that combines 1H-NMR and principal component analysis (PCA) was employed to obtain the quality evaluation of biopharmaceuticals, with regard to their quality, consistency, and differences in protein modification patterns. To assess the feasibility of the method, three 1H-NMR spectra of oxytocin (OXT) were collected every 7 d (at Day 0, 7 and 14), and time-dependent changes in the spectra were found by PCA of the 1H-NMR signals from 0.5—9.0 ppm, excluding the region around the water signal (4.6—5.0 ppm). Although the three OXT spectra seemed similar by simple visual inspection, time-dependent differences among the three spectra were clearly distinguished by a PCA scores plot. Peak changes indicating both OXT decomposition and the emergence of new OXT decomposition products within the timeframe of the experiment were also observed by a PCA loading plot. The results demonstrate that this method can evaluate the consistency of biopharmaceutical quality.
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