Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 60 , Issue 7
Showing 1-19 articles out of 19 articles from the selected issue
Review
  • Hiromi Hamamoto
    Type: Review
    2012 Volume 60 Issue 7 Pages 799-817
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    This review describes our recent efforts in the development and application of new oxidation systems utilizing oxometalate catalysts. The novel use of heteropoly acid (HPA), an acidic oxometalate catalyst, in hypervalent iodine-mediated oxidations provided an effective strategy to generate cation radical species that enables a variety of direct C–H functionalizations of aromatic compounds. This strategy brought a facile biaryl synthesis and new spirodienone syntheses in aromatic oxidation chemistry. Moreover, this strategy opens up a facile synthetic route to morphinandienone alkaloids. On the other hand, the use of oxometalate catalyst together with poly(N-isopropylacrylamide) (PNIPAAm)-based polymer in the development of new solid-phase catalyst provided a novel reaction system in water. Due to the characteristic temperature-responsive intelligence of PNIPAAm, this reaction system brought a remarkable acceleration of the reactivity and ease of catalyst recovering in catalytic oxidation that uses hydrogen peroxide or oxygen gas (O2) as primary oxidant. In addition, the recovered solid-phase catalyst could be used for consecutive reactions without any significant loss of its catalytic efficacy.
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Regular Articles
  • Mahesh Kumar Talari, Abu Bakar Abdul Majeed, Dulal Krishna Tripathi, M ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 818-824
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    The application of nanomaterials has gained considerable momentum in various fields in recent years due to their high reactivity, excellent surface properties and quantum effects in the nanometer range. The properties of zinc oxide (ZnO) vary with its crystallite size or particle size and often nanocrystalline ZnO is seen to exhibit superior physical and chemical properties due to their higher surface area and modified electronic structure. ZnO nanoparticles are reported to exhibit strong bacterial inhibiting activity and silver (Ag) has been extensively used for its antimicrobial properties since ages. In this study, Ag doped ZnO nanoparticles were synthesized by mechanochemical processing in a high energy ball mill and investigated for antimicrobial activity. The nanocrystalline nature of zinc oxide was established by X-ray diffraction (XRD) studies. It is seen from the XRD data obtained from the samples, that crystallite size of the zinc oxide nanoparticles is seen to decrease with increasing Ag addition. Field emission scanning electron microscopy (FESEM) and transmission electron microscopy (TEM) data also supported the nanoparticle formation during the synthesis. The doped nanoparticles were subjected to antimicrobial investigation and found that both increase in Ag content and decrease in particle size contributed significantly towards antimicrobial efficiency. It was also observed that Ag doped ZnO nanoparticles possess enhanced antimicrobial potential than that of virgin ZnO against the studied microorganisms of Escherichia coli and Staphylococcus aureus.
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  • Keishi Kawata, Takehisa Hanawa, Naoko Endo, Masahiko Suzuki, Toshio Og ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 825-830
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    In the present study, all-trans retinoic acid (RA) gels formulated with various compositions of polyethylene oxide (Emulgen®) and iota-carrageenan (ι-CG) were prepared and their physicochemical properties were evaluated. The compression energy, which is the work required to compress the product through a fixed distance, increased with increasing amount of ι-CG or Emulgen®. The adhesion energy and displacement decreased with increasing amount of ι-CG or Emulgen® due to the progression of gel formation. From the results of the sensory tests, the properties of RA gels such as adhesiveness, gel strength and spreadability seemed to be adjustable depending on the condition of skin by varying the components of RA gels. Through photostability study, the expiration date and storage conditions of RA gels were determined as “4°C for 28 d with no exposure to light.”
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  • Jin Hisazumi, Tatsuya Suzuki, Naoki Wakiyama, Hiroaki Nakagami, Katsuh ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 831-836
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    The purpose of this research is to investigate the topographical pattern of hydration and dehydration (also known as pseudo-polymorphic change) of drug substance in drug product using terahertz (THz) pulsed imaging. Emphasis is placed on (1) applicability of THz pulsed imaging and (2) kinetic analysis in the pseudo-polymorphic change. Either anhydrous or monohydrated form of theophylline was used as the drug substance, leading to initially anhydrous or monohydrated tablets. These tablets were stored at 25°C to keep the relative humidity constant at 84% (anhydrous tablets) or 45% (monohydrated tablets), respectively. The THz pulsed imaging was confirmed to enable visualization that the hydration of the anhydrous form or the dehydration of the monohydrated form began on the surface of the tablets and gradually progressed to the core side in the tablets with storage. Kinetic studies indicated that these pseudo-polymorphic changes followed the phase boundary mechanism. Since the other imaging techniques has been scarcely achieved to show the topographical pattern of pseudo-polymorphic change of drug substances in drug products directly and visually, it is considered that THz pulsed imaging has a potential ability to solve complicated issues in pharmaceutical development.
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  • Caiqin Yang, Xiujuan Xu, Jing Wang, Zhiqian An
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 837-845
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    The solid dispersion (SD) technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs. In the present work, SDs of the Ca2+ channel blocker dipfluzine (DF) with polyvinylpyrrolidone K30 (PVP) and poloxamer 188 (PLXM) were prepared by the powder solid co-grinding method under a solvent-free condition. The properties of all SDs and physical mixtures were investigated by X-ray diffraction, Fourier-transform infrared, differential scanning calorimetry, scanning electron microscopy, dissolution test, and particles size determination. Eutectic compounds were produced between the DF and PLXM matrix during the co-grinding process, whereas glass suspension formed in the SDs with PVP carrier. Hydrogen bond formation was not observed between DF and carriers and DF was microcrystalline state in the PVP and PLXM matrices. The solubility of DF in different concentration of carriers at 25, 31, and 37°C was investigated; the values obtained were used to calculate the thermodynamic parameters of interaction between DF and carriers. The Gibbs free energy (ΔrGθ) values were negative, indicating the spontaneous nature of dispersing DF into the carriers. Moreover, entropy is the drive force when DF disperses into the matrix of PVP, while, enthalpy-driven dispersing encounters in the PLXM carrier. All the SDs of DF/carriers showed a considerably higher dissolution rate than pure DF and the corresponding physical mixtures. The cumulative dissolution rate at 10 min of the SD with a 1 : 3 DF/carrier ratio increased 5.1-fold for PVP and 5.5-fold for PLXM.
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  • Junichi Odo, Sei-ichi Torimoto, Suguru Nakanishi, Tomoya Niitani, Hiro ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 846-853
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    The photodegradation of environmental mutagens, such as 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeAαC), and 2-amino-3-methyl-imidazo[4,5-f]quinoline (IQ), was investigated by visible irradiation in the presence of xanthene dyes as photosensitizers. Although the environmental mutagens themselves were very stable during visible irradiation under the conditions in this study, they were effectively photodegraded in the presence of the xanthene dyes (erythrosine, rose bengal, and phloxine). Moreover, photodegradation of the mutagens was further enhanced for xanthene dyes loaded onto a water-soluble diethylaminoethyl (DEAE)-dextran anion-exchanger via ionic interactions (xanthene-dyeDEX). Photodegradation was inhibited by O2 removal from the reaction solution. In ESR spin-trapping experiments using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a trapping reagent, signals characteristic of DMPO-OH (hydroxyl radical) were observed in the presence of xanthene-dyeDEX. These results suggest that reactive oxygen species derived from O2, such as singlet molecular oxygen (1O2) and/or OH, were active participants in photodegradation of the mutagens in the presence of xanthene dyes or xanthene-dyeDEX.
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  • Mekala Rajasekhar, Kunda Uma Maheswara Rao, Chereddy Syama Sundar, Nem ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 854-858
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    A simple and efficient one pot synthesis of 2-amino-4H-chromen-4-yl phosphonate derivatives has been accomplished by the condensation of salicylaldehyde, malononitrile/ethylcyanoacetate and triethyl phosphite/trimethyl phosphite in the presence of molecular iodine as catalyst in water at room temperature. All the reactions were very clean and the products were obtained in very good to excellent yields. The title compounds are characterized by IR, 1H-, 13C-, 31P-NMR and mass spectra, also studied their antimicrobial and antioxidant activity.
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  • Shobha Churi, Madhan Ramesh, Krunal Bhakta, Jacob Chris
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 859-864
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    The objective of this study was to assess the patterns, severity and clinical outcome of poisoning incidents. A prospective assessment was conducted over a period of 1 year in tertiary-care teaching hospitals. Glasgow coma scale (GCS), poisoning severity score (PSS), and snake bite severity score (SSS) were used to predict the severity of poisoning, and then compared to the clinical outcome. The study involved 212 patients with a mean age of 26.7±12.7 years. Pesticides were found to be the most common poisoning agents. The incidents of intentional poisoning (n=178) were higher than accidental (n=34) poisoning. Poisoning incidents were higher in male population (n=132) compared to female population (n=80). The poisoning incidents were predominantly higher among literates (n=155). The poisoning incidents were higher in rural areas (n=129), followed by urban (n=53) and semi-urban (n=30) areas. The poisoning incidents were highest in the middle class population (n=108), followed by poor class (n=101) and rich class (n=3) population. A majority of patients whose severity of illness was predicted to be mild to moderate recovered from the poisoning. In contrast, patients whose illness was predicted to be severe were either discharged with severe morbidity or deceased. There was a moderate correlation between GCS and PSS scoring systems (r=0.51, p<0.001).
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  • Bojan Božić, Jelena Rogan, Dejan Poleti, Nemanja Trišov ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 865-869
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    A series of novel Mn(II), Co(II), Ni(II), Cu(II) and Zn(II) complexes with oxaprozin (Hoxa), a non-steroidal anti-inflammatory drug, has been synthesized. The drug and complexes have been characterized by elemental and thermogravimetric (TG) analysis, Fourier transform (FT)-IR, 1H-NMR, 13C-NMR, UV-Vis spectroscopy and magnetic susceptibility measurements. The (pseudo)octahedral geometry has been proposed for all complexes based on electronic spectra and magnetic moments. With exception of the Cu(II) complex, where bridging bidentate mode of COO groups has been found, FT-IR spectra confirmed chelately coordinated COO groups in the other complexes. The general formula of the complexes is [M(H2O)2(oxa)2xH2O, with x=2 for M=Mn, Co and Ni and x=1.5 for Zn. The binuclear Cu(II) complex, [Cu2(H2O)2(OH)(oxa)3]·2H2O, has strong Cu–Cu interactions of antiferromagnetic type. The complexes and Hoxa did not exhibit the cytotoxic effect to peritoneal macrophages. For the first time these complexes have been tested for their in vitro antiproliferative activity against human colon and breast cancer cell lines, HCT-116 and MDA-231, respectively. For all investigated compounds significant antiproliferative effects have been observed. Ni(II) complex has been shown to be a promising antiproliferative agent exerting excellent activity against HCT-116 even in nanomolar concentrations.
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  • Toshiyuki Niwa, Daisuke Mizutani, Kazumi Danjo
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 870-876
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    Particles of poorly water-soluble drugs were prepared to develop a dry powder inhaler (DPI). Spray freeze-drying (SFD) technique using a four-fluid nozzle (4N), which has been developed by authors, was applied in this research. Ciclosporin and mannitol were used as a poorly water-soluble model drug and a dissolution-enhanced carrier, respectively. The organic solution of ciclosporin and aqueous solution of mannitol were separately and simultaneously atomized through the 4N, and the two solutions were collided with each other at the tip of the nozzle edge. The spray mists were immediately frozen in liquid nitrogen to form a suspension. Then, the iced droplets were freeze-dried to prepare the composite particles of the drug and carrier. tert-Butyl alcohol (t-BuOH) was used as the organic spray solvent due to its relatively high freezing point. The resultant composite particles with varying drug content were characterized depending on their morphological and physicochemical properties. The particles contained amorphous ciclosporin and δ-crystalline mannitol. The characteristic porous structure of SFD particles potentially contributed to their good aerodynamic performance. A series of particles with a similar size distribution and different drug content revealed that the incorporation of mannitol successfully improved the cohesive behavior of ciclosporin, leading to enhanced aerosol dispersion. The dissolution test method using low-volume medium was newly established to simulate the release process from particles deposited on the surface of the bronchus and pulmonary mucosa. The composite with hydrophilic mannitol dramatically improved the in vitro dissolution behavior of ciclosporin in combination with the porous structure of SFD particles.
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  • Fumika Yakushiji, Hironari Tanaka, Kyohei Muguruma, Takahiro Iwahashi, ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 877-881
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    Plinabulin (1) is a potent anti-microtubule agent, however, its low water solubility has to be improved for the advantage in pharmacokinetics and chemotherapy. In this report, the replaceable water-solubilizing moiety of the water-soluble prodrug of plinabulin (1) was investigated. The properties of the water-soluble prodrugs of plinabulin (1), in which the water-solubilizing part was replaced with a new functionality, were evaluated. The newly introduced water-solubilizing moiety provided interesting effects on the water solubility and half-life of the prodrugs.
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  • Jun Chiba, Fumihito Muro, Masaki Setoguchi, Nobuo Machinaga
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 882-886
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    This contribution describes a concise synthesis to ethyl trans-[(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylate (2b) as a key intermediate of very late antigen-4 (VLA-4) antagonist trans-4-[1-[[2,5-dichloro-4-(1-methyl-3-indolylcarboxyamide)phenyl]acetyl]-(4S)-methoxy-(2S)-pyrrolidinylmethoxy]cyclohexanecarboxylic acid (1). The synthesis employs a reductive etherification as a key reaction using (2S,4S)-1-benzyloxycarbonyl-4-methoxypyrrolidine-2-carboxyaldehyde (12) and trans-4-triethylsilyloxycyclohexanecarboxilic acid ethyl ester (13b). This synthesis provides 2b in 6 steps with 38% overall yield from commercially available starting material.
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  • Zhen-Hua Luo, Shuang-Yan He, Bao-Quan Chen, Yan-Ping Shi, Yu-Ming Liu, ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 887-891
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    A series of novel 1,3,4-oxadiazole derivatives based on benzisoselenazolone has been prepared and tested for antiproliferative activity in vitro against the cells of human cancer cell lines: SSMC-7721 (human liver cancer cell), MCF-7 (human breast cancer cell) and A549 (human lung cancer cell). All the compounds obtained exhibited antiproliferative activity and showed selective cytotoxicity against different cancer cells. Compounds 7d and 7i showed significant antiproliferative activities against MCF-7 cells, with IC50 values of 1.07 and 1.76 µM respectively. Compound 7d were found to be the most potent compound against SSMC-7721 cells, with IC50 values 4.46 µM.
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  • Masanori Kuroyanagi, Miki Murata, Takahisa Nakane, Osamu Shirota, Sets ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 892-897
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    In the course of screening for leishmanicidal constituents from Asian and South American medicinal plants, a Pakistani medicinal plant, Withania coagulans, showed activity. We therefore studied the active components of the methanol extract of aerial parts of W. coagulans. From the ethyl acetate soluble fraction of the extract, four new withanolides (14) were isolated along with seven known withanolides (511). The new compounds were elucidated to be (14R,15R,17S,20S,22R)-14,15,17,20-tetrahydroxy-1-oxowitha-2,5,24-trienolide (1), (14R,15R,17S,20S,22R)-14,15,17,20-tetrahydroxy-1-oxowitha-3,5,24-trienolide (2), (14S,17R,20S,22R)-14,17,20-trihydroxy-1-oxowitha-2,5,24-trienolide (3), and (14S,17R,20S,22R)-14,17,20-trihydroxy-1-oxowitha-3,5,24-trienolide (4), from 1H-NMR, 13C-NMR, 2D-NMR and high resolution (HR)-MS data. Some of these compounds having the partial structure 1-oxo-2,5-diene showed strong leishmanicidal activity against Leishmania major.
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  • Masaki Ohtawa, Kouhei Sugiyama, Tohru Hiura, Shujiro Izawa, Kazuro Shi ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 898-906
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    The stereoselective total synthesis of atpenins A4 (2) and B (3), harzianopyridone (4), and NBRI23477 B (5) have been developed using a convergent approach involving the coupling reaction of a common iodopyridine with an aldehyde corresponding to the appropriate side chain of the desired compound. Furthermore, the absolute configurations of atpenin B (3), harzianopyridone (4), and NBRI23477 B (5) have been unambiguously determined.
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  • Hikaru Fujita, Munetaka Kunishima
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 907-912
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    A method for one-pot synthesis of oxazol-5(4H)-ones has been developed using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM), which is available for the activation of carboxylic acids in an aqueous solvent. The oxazolones were prepared by the N-acylation of amino acids with carboxylic acids and the subsequent cyclodehydration of the resulting N-acylamino acids by the addition of N,N-diethylaniline. Since both these reactions proceed effectively with the same coupling reagent, DMT-MM, in aqueous solvents, the procedure is simplified and becomes easy to perform. In addition, 5-(triazinyloxy)oxazole derivatives have been synthesized by controlling the basicity of the reaction system.
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  • Shin-ichiro Kurimoto, Kyoko Suzuki, Mamoru Okasaka, Yoshiki Kashiwada, ...
    Type: Regular Article
    2012 Volume 60 Issue 7 Pages 913-919
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    Seven new sesquiterpene lactone glycosides (17) were isolated from the H2O-soluble fraction from the MeOH extract of the roots of Ferula varia. Their structures were elucidated by extensive spectroscopic analyses. The absolute configurations of compounds 1 and 2 were determined by modified Mosher’s method.
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Notes
  • Guo-Cai Wang, Xiao-Li Zhang, Yi-Fei Wang, Guo-Qiang Li, Wen-Cai Ye, Ya ...
    Type: Note
    2012 Volume 60 Issue 7 Pages 920-923
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    Phytochemical investigation of the roots of Wikstroemia indica led to the isolation of four new dilignans (14). Their structures were established on the basis of the spectroscopic data including UV, IR, high resolution-electron ionization-mass spectrometry (HR-ESI-MS), 1D- and 2D-NMR (1H–1H correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC) and rotating frame Overhauser enhancement spectroscopy (ROESY)). These dilignans were screened for their in vitro antiviral activities against respiratory syncytial virus (RSV) with cytopathic effect (CPE) reduction assay.
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  • Chien-Chang Shen, Kun-Yuan Hong, Jennifer Chen, Li-Jie Zhang, Zhi-Hu L ...
    Type: Note
    2012 Volume 60 Issue 7 Pages 924-929
    Published: July 01, 2012
    Released: July 01, 2012
    JOURNALS FREE ACCESS
    From the ethanolic extract of Quercus glauca, two new lignans, (+)-5′-methoxyisolariciresinol-9′-O-α-L-rhamnopyranoside (1) and (7R,8S)-dihydrodehydrodiconiferyl alcohol 4-β-D-xyloside (2), along with fourteen known compounds including four lignanoids (36), five triterpenoids (711), two flavonoids (12, 13), two aromatics (14, 15), and one steroid (16) were isolated. The structures of the new compounds were elucidated on the basis of spectroscopic analysis. Moreover, compounds 9 and 14 strongly inhibited nitric oxide (NO) production with IC50 values of 8.25 and 14.04 µM, respectively, and compounds 1, 46, 14, and 15 showed moderate antioxidant activities.
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