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Volume 61, Issue 1
Displaying 1-17 of 17 articles from this issue
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Regular Articles
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Miyako Yoshida, Yuko Takasu, Kaori Shimizu, Keiichi Asahara, Takahiro ...2013 Volume 61 Issue 1 Pages 1-7
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
Advance online publication: November 02, 2012JOURNAL FREE ACCESSThe purpose of this study was to predict the stability of imipenem in a mixed infusion. The hydrolysis of imipenem in aqueous solution was found to be accelerated by pH, and by increasing concentrations of sodium bisulfite (SBS) and L-cysteine. Equations were derived for the degradation rate constants (kobs) of pH, SBS and L-cysteine and fractional rate constants were estimated by nonlinear least-squares method (quasi-Newton method using the solver in Microsoft Excel) at 25°C. The activation energy (Ea) and frequency factor (A) were calculated using the Arrhenius equation. The pH of the mixed infusion was estimated using the pH characteristic (PHC) curve. From these results, an equation was derived giving the residual ratio (%) of imipenem at any time after mixing an infusion containing SBS and/or L-cysteine at any temperature and at pH 4.0–10.0. A high correlation was shown to exist between the estimated and determined residual ratios (%).View full abstractDownload PDF (932K) -
Yukako Ito, Noriyuki Hamasaki, Hirofumi Higashino, Yuki Murakami, Nao ...2013 Volume 61 Issue 1 Pages 8-15
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSTo increase the absorbed amount of a drug from dissolving microneedles (DMs), three DM array chips were prepared in which (1) the drug was localized at the acral portion of DMs, (2) the drug was loaded in each whole DM, and (3) the drug was loaded in DMs and the chip. Fluorescein free form (FL) and its sodium salt (FLNa) were used as model drugs. The DM array chip had 15-mm diameter with 225 DMs, each 500-µm long with a 300-µm diameter base. The respective FLNa contents in the three chips were (1) 0.18±0.03, (2) 0.64±0.07, and (3) 10.95±1.07 mg. The FL contents were (1) 0.20±0.01, (2) 0.68±0.03 and (3) 12.47±1.01 mg. The in vitro release of fluorescein from FLNa DMs was faster than that from FL DMs. In vitro permeability experiments showed that (3) produced the greatest increase in the permeability of fluorescein through rat skin, especially in FLNa loaded DMs. In vivo rat absorption study by application of DM array chips to the rat abdominal skin for 6 h demonstrated that the systemically absorbed amount of fluorescein increased from 0.18±0.02 mg, 0.53±0.19 mg, to 5.38±1.99 mg from systems (1) and (2)–(3). By decreasing the application time of DMs to the rat skin, the absorbed amount of fluorescein decreased along with the application time. The physiological state of the skin recovered within 30 min after chip removal. Using a type (3) DM array chip, more than 1.0 mg of water-soluble drug can be delivered to the systemic circulation.View full abstractDownload PDF (1405K) -
Sai-Sai Xie, Xiao-Bing Wang, Jiang-Yan Li, Ling-Yi Kong2013 Volume 61 Issue 1 Pages 16-24
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSStudy on the pharmacophore model of α1-adrenoceptor (α1-AR) antagonists led to design a series of novel 7-mercaptocoumarin derivatives as α1-AR antagonists. All designed compounds have been synthesized and biologically evaluated. The results showed that most of them exhibited strong antagonistic activity. Especially compound 6 showed excellent activity, which was better than that of the reference compound prazosin. Structure–activity relationship studies revealed that small hydrophobic group at the terminal heterocyclic ring and ortho substituents on the phenyl ring of phenylpiperazine moiety were the essential structural factors for α1-AR antagonistic activity. The pharmacophore modeling studies further clarified their structural contributions to antagonistic activity and also demonstrated that 7-mercaptocoumarin moiety could be a useful scaffold for design of α1-AR antagonists.View full abstractDownload PDF (951K) -
Venkata Ramana Katla, Rasheed Syed, Chandra Sekhar Kuruva, Hema Kumar ...2013 Volume 61 Issue 1 Pages 25-32
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSA series of novel guanidine derivatives were synthesized in three steps and their anti-inflammatory activities in vitro and in vivo evaluated. 2-Aminopyridin-3-ol (1) was reacted with thiophosphoryl chloride (2) to give a monochloride (3). It was further reacted with cyanamide to afford the corresponding cyanamine (4), which was subsequently reacted with different heterocyclic amines to form the title compounds (5a–l). The substituent in the guanidine function affected the potency of anti-inflammatory activity. The compounds having benzothiazole, fluorophenyl, and piperazinyl moieties enhanced the anti-inflammatory activity.View full abstractDownload PDF (794K) -
Atsuko Tada, Kana Takahashi, Kyoko Ishizuki, Naoki Sugimoto, Takako Su ...2013 Volume 61 Issue 1 Pages 33-38
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
Advance online publication: November 01, 2012JOURNAL FREE ACCESSThe extract prepared from the leaves of Stevia rebaudiana BERTONI (Asteraceae) contains sweet steviol glycosides, mainly stevioside and rebaudioside A. Highly purified stevia extracts have become popular worldwide as a natural, low-calorie sweetener. They contain various types of steviol glycosides, and their main components are stevioside and rebaudioside A. The content of each steviol glycoside is quantified by comparing the ratios of the molecular weights and the chromatographic peak areas of the samples to those of stevioside or rebaudioside A standards of the Food and Agriculture Organization of the United Nations (FAO)/World Health Organization (WHO) Joint Expert Committee on Food Additives (JECFA) and other specifications. However, various commercial standard reagents of stevioside and rebaudioside A are available. Their purities are different and their exact purities are not indicated. Therefore, the measured values of stevioside and rebaudioside A contained in a sample vary according to the standard used for the quantification. In this study, we utilized an accurate method, quantitative NMR (qNMR), for determining the contents of stevioside and rebaudioside A in standards, with traceability to the International System of Units (SI units). The purities of several commercial standards were determined to confirm their actual values.View full abstractDownload PDF (1081K) -
Tadashi Norioka, Yoshihiro Hayashi, Yoshinori Onuki, Hirotaka Andou, D ...2013 Volume 61 Issue 1 Pages 39-49
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSA novel approach to establishing the design space for the oral formulation manufacturing process was investigated. A response surface method incorporating multivariate spline interpolation was applied to overcome the nonlinear problem, which is always problematic in pharmaceutical development studies, and a bootstrap resampling technique, polynomial approximation technique, and 95% confidence intervals based on a nonparametric approach were applied to estimate the reliability of the established design space derived from the nonlinear response surface model. The critical quality attributes (CQAs) of intermediate material rather than the critical process parameters (CPPs) were chosen as the causal factors for the response variables, which were CQAs of the final product to avoid scale-gap and equipment-gap. This enabled the effective use of data sets accumulated during all pharmaceutical development studies. It was confirmed that a conservative border as well as an optimistic border of the design space for practical use was obtained considering the variability of the border of the design spaces on nonlinear response surfaces. Furthermore, the nonlinear response surface model using CQAs of intermediate material derived from data sets of a laboratory scale study and pilot scale studies could predict the CQA of the final product (2.5 h dissolution of commercial-scale study) with high accuracy. Consequently, the proposed novel approach overcame all of the difficulties for the manufacturing process development of oral formulations and this is the first study to demonstrate the effectiveness of the design space using CQA of intermediate material for the oral formulation manufacturing process.View full abstractDownload PDF (1966K) -
Mohammed Salem Al-Dosari, Mostafa Mohamed Ghorab, Mansour Sulaiman Al- ...2013 Volume 61 Issue 1 Pages 50-58
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSBased on the reported anticancer activity of quinolines, a new series of 7-chloroquinoline derivatives bearing the biologically active benzenesulfonamide moiety 2–17 and 19–25 were synthesized starting with 4,7-dichloroquinolne 1. Compound 17 was the most active compound with IC50 value 64.41, 75.05 and 30.71 µM compared with Doxorubicin as reference drug with IC50 values 82.53, 88.32 and 73.72 µM on breast cancer cells, skin cancer cells and neuroblastoma, respectively. All the synthesized compounds were evaluated for their in vitro anticancer activity on breast cancer cells, skin cancer cells and neuroblastoma cells. Most of the synthesized compounds showed moderate activity. In order to suggest the mechanism of action for their cytotoxic activity, molecular docking for all synthesized compounds was done on the active site of phosphoinositide kinase (PI3K) and good results were obtained.View full abstractDownload PDF (1066K) -
Katsumi Nishimura, Shinji Horii, Takao Tanahashi, Yumi Sugimoto, Jun Y ...2013 Volume 61 Issue 1 Pages 59-68
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
Advance online publication: October 29, 2012JOURNAL FREE ACCESSBisbenzylisoquinoline alkaloid, nelumboferine which was recently isolated from the embryo of Nelumbo nucifera, and stereoisomers of neferine, which is a major alkaloid of the embryo of N. nucifera, were stereoselectively synthesized. Pharmacological activity of nelumboferine, stereoisomers of neferine, liensinine, isoliensinine, and O-methylneferine were evaluated.View full abstractDownload PDF (1552K) -
Reiko Nishino, Takuya Hayakawa, Tadanobu Takahashi, Takashi Suzuki, Ma ...2013 Volume 61 Issue 1 Pages 69-74
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSNovel sialidase inhibitors 11 having an α-acylaminoamido group at the C-4 position of Neu5Ac2en 1 against human parainfluenza virus type 1 (hPIV-1) were synthesized using one-pot isocyanide-based four-component condensation, and their inhibitory activities against hPIV-1 sialidase were studied. Compound 11b showed inhibitory activity (IC50=5.1 mM) against hPIV-1 sialidase. The degree of inhibition of 11b was much weaker than that of 1 (IC50=0.3 mM).View full abstractDownload PDF (762K)
Notes
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Yao Zhang, Jun-Song Wang, Xiao-Bing Wang, Yu-Cheng Gu, Ling-Yi Kong2013 Volume 61 Issue 1 Pages 75-81
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESS
Supplementary materialTwo new apo-tirucallane triterpenoids with six-membered hemiketal, polystanins A (1) and B (2), and two new tirucallane triterpenoids, polystanins C (3) and D (4) were isolated from the fruits of Aphanamixis polystachya. They were elucidated on the basis of detailed spectroscopic analysis including IR, high resolution-electrospray ionization (HR-ESI)-MS, 1 dimensional (1D)- and 2D-NMR. Their absolute configurations were determined by a combination of modified Mosher’s method, and electronic circular dichroism (ECD) calculation.View full abstractDownload PDF (806K) -
Rina Miyake, Tomohiro Uchimura, Xu Li, Totaro Imasaka2013 Volume 61 Issue 1 Pages 82-84
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESS
Supplementary materialFluorescence lifetime imaging microscopy (FLIM) was used to monitor the interaction between androgen receptor (AR) tagging of a green fluorescent protein (GFP) and the ligands in living cells. The fluorescence lifetime of the AR-GFP without ligands was ca. 3.1 ns, which was reduced to ca. 2.5 ns after treatment with agonist 5α-dihydrotestosterone. On the other hand, the fluorescence lifetime of AR-GFP was not changed after treatment with antagonist hydroxyflutamide. The reaction kinetics was simulated in the present study, and the obtained results indicated the possibility of the presence of an intermediate complex during the reaction. FLIM can be used to record the ratio of the AR as it reacts with an agonist, and, therefore, it is useful for acquiring information concerning the interaction between AR and ligands in living cells.View full abstractDownload PDF (620K) -
Yuta Takahashi, Shizuyo Horiyama, Chie Honda, Kiyoko Suwa, Kazuki Naka ...2013 Volume 61 Issue 1 Pages 85-89
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESS
Supplementary materialCigarette smoke, a collection of many toxic chemicals, contributes to the pathogenesis of smoking-related diseases such as chronic obstructive pulmonary disease and cancer. Much work has been done on the chemical analysis of ingredients in cigarette smoke, but there are few reports on the active ingredients that can modify biomolecules. We used a sensitive liquid chromatography-mass spectrometry (LC/MS) and LC/MS/MS method to show that L-tyrosine (Tyr), an amino acid with a highly reactive hydroxyl group, readily reacts with cigarette smoke extract (CSE) at body temperature (37°C) to form various Tyr derivatives. Among these derivatives were N-(3-oxobutyl)-Tyr and two acetylated compounds, N-acetyl-Tyr and O-acetyl-Tyr, which were synthesized by reaction of Tyr with methyl vinyl ketone and acetic anhydride, respectively, at 37°C. The presence of methyl vinyl ketone and acetic anhydride in CSE was confirmed by gas chromatography-mass spectrometry (GC/MS). These results indicate that Tyr can easily react with active ingredients in CSE. The present analytical methods should aid the search for active ingredients in cigarette smoke.View full abstractDownload PDF (459K) -
Xu Liu, Rui Zhan, Wei-Guang Wang, Xue Du, Xiao-Nian Li, Jian-Hong Yang ...2013 Volume 61 Issue 1 Pages 90-95
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSFive new ent-abietane diterpenoids, ent-abierubesins A–E (1–5), and two new ent-kauranoids, hubeirubesins A and B (6, 7), together with three known diterpenoids (8–10), were isolated from the aerial parts of Isodon rubescens. Their structures were identified by means of extensive spectroscopic analysis, and the absolute stereochemistry of 1 was determined by single-crystal X-ray diffraction experiment.View full abstractDownload PDF (892K) -
Cheng-Qin Liang, Jing Hu, Yi-Ming Shi, Shan-Zhai Shang, Xue Du, Rui Zh ...2013 Volume 61 Issue 1 Pages 96-100
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSFive new dibenzocyclooctadiene lignans, schisphenlignans A–E (1–5), together with eight known ones, were isolated from the stems of Schisandra sphenanthera. The structures of 1–5 were elucidated based on the analysis of their NMR, MS and circular dichroism (CD) spectra. Some isolates were tested for their acute activities on insulin sensitivity in 3T3-L1 differentiated adipocytes, but none of them showed significant bioactivity with 10 µM administration of the tested compounds.View full abstractDownload PDF (635K) -
Guoxu Ma, Wenjie Guo, Lizi Zhao, Qingxia Zheng, Zhaocui Sun, Jianhe We ...2013 Volume 61 Issue 1 Pages 101-104
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSTwo new triterpenoid saponins, named platycodon A (3-O-β-D-glucopyranosyl-16-O-β-D-glucopyranosyl-2β,3β,16β,21β-tetrahydroxyolean-12-en-28-oic acid) and platycodon B (3-O-β-D-glucopyranosyl-16-O-β-D-xylopyranosyl-2β,3β,16β,21β-tetrahydroxyolean-12-en-28-oic acid) were isolated from the roots of Platycodon grandiflorum. The structures of these compounds were elucidated by means of various spectroscopic analyses. Compounds 1 and 2 were tested in HepG-2, A549 and DU145 human cancer cell lines and showed remarkable cytotoxic activities against HepG-2 and A549 cancer cell lines with IC50 values ranging from 4.9 to 9.4 µM, but they displayed weak cytotoxic activities against DU145 cancer cell line with IC50 values greater than 10 µM.View full abstractDownload PDF (455K) -
Toshiyuki Kuwana, Mitsue Miyazaki, Hikaru Kato, Sachiko Tsukamoto2013 Volume 61 Issue 1 Pages 105-107
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
JOURNAL FREE ACCESSThree new himeic acids E–G were isolated from a marine-derived fungus, Aspergillus sp., and their structures were determined by spectroscopic analysis. Although himeic acid A inhibited the activity of ubiquitin-activating enzyme (E1), the three new derivatives did not.View full abstractDownload PDF (372K) -
Akiko Nakata, Kenichi Kobayashi, Hiroshi Kogen2013 Volume 61 Issue 1 Pages 108-110
Published: January 01, 2013
Released on J-STAGE: January 08, 2013
Advance online publication: October 19, 2012JOURNAL FREE ACCESSWe have established an efficient method for preparing methyl bis(2,2,2-trifluoroethoxy)bromophosphonoacetate, which we developed for the stereoselective synthesis of (E)-α-bromoacrylates. This improved method enables the reagent to be prepared reproducibly in one step from methyl bis(2,2,2-trifluoroethoxy)phosphonoacetate.View full abstractDownload PDF (3006K)
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