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Volume 60, Issue 5
Displaying 1-16 of 16 articles from this issue
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Regular Articles
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Lu Lu, Jian-Chao Chen, Yan Li, Chen Qing, Yuan-Yuan Wang, Yin Nian, Mi ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 571-577
Published: 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSTwo new triterpenoids and a chromone glycoside, namely, 24-epi-cimigenol-3-one (1), foetinoside (2), cimifugin-4′-O-[6″-feruloyl]-β-D-glucopyranoside (3), together with 18 known compounds, were isolated from the rhizomes of Cimicifuga foetida L. collected in Guizhou Province, China. All of the compounds were identified by spectroscopic methods, as well as chemical methods. In the in vitro cytotoxicity evaluation of these compounds against 5 human cancer cell lines, cimigenol (8) exerted the most potent cytotoxic activity against SMMC-7721 (7.87 µM) and A-549 (12.16 µM), while cimiacerin B (9) also showed obvious cytotoxicity against the A-549 cell line, with an IC50 value of 16.77 µM.View full abstractDownload PDF (874K) -
Gülay Dilek Çelik, Ali Dişli, Yağmur Öner, ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 578-582
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSA series of 6-thiocyanatopurine derivatives introduced with different alkyl groups in position 9 was synthesized. The structures of the synthesized compounds were evaluated via spectroscopic methods and elemental methods of analyses. All the synthesized compounds were screened for their antibacterial activities against Gram-positive and Gram-negative bacteria and for their antifungal activities against yeast strains. All the synthesized compounds showed better antibacterial activities against Gram-positive bacteria compared to Gram-negative bacteria. DNA interactions with pBR322 DNA were determined. Most of the compounds caused conformational changes in DNA.View full abstractDownload PDF (804K) -
Figen Tirnaksiz, Ayşegül Kayiş, Nevin Çelebi, Es ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 583-592
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSThe aim of this study was to prepare a topical water-in-oil type microemulsion containing metronidazole and to compare its effectiveness with a commercial gel product in the treatment of rosacea. A pseudo-ternary phase diagram (Km=2 : 1) was constructed using lecithin/butanol/isopropyl myristate/water. The microemulsion was chosen from the microemulsion region in the phase diagram. The formulation was a water-in-oil type microemulsion (droplet size: 11.6 nm, viscosity: 457.3 mPa·s, conductivity: 1.5 µs/cm, turbidity: 6.89 NTU) and the addition of the metronidazole did not alter the properties of the system. The release experiment showed that the release rate of metronidazole from the commercial gel product was higher than that of the microemulsion. Stability experiments showed that the metronidazole microemulsion remained stable for at least 6 months; none of the characteristic properties of the microemulsion had changed, the system retained its clarity and there was no sign that crystallization of metronidazole has occurred. Microemulsion was compared to a gel product in a randomized, double-blind, baseline-controlled, split-face clinical trial for the treatment of patients. After the 6-week treatment period there was a statistically significant difference in reduction of the main symptoms of rosacea. Of the patients treated with the microemulsion, 17% experienced complete relief from inflammatory lesions, and 50% from erythema. The microemulsion resulted in complete relief in 38% of the patients with telangiectasia while the commercial product did not provide any relief of telangiectasia symptoms. In conclusion, the microemulsion containing metronidazole was found to be more effective in reducing the symptoms of rosacea compared to the commercial gel product.View full abstractDownload PDF (610K) -
Saburo Murata, Takashi Izumi, Hideki ItoArticle type: Regular Article
2012 Volume 60 Issue 5 Pages 593-597
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSThe spray performance of the new Stmerin® D pressurized metered dose inhalers (MDIs), prescribed for asthma treatment, was previously reported to be sensitive to moisture content in the canister. In this formulation, active ingredients were suspended in hydrofluoroalkanes (HFA-134a and HFA-227). Here, we report on the critical moisture content of a new MDI formulation using HFA-227. We prepared MDIs with different moisture contents (107–331 ppm) and investigated the effect of moisture content on the fine particle dose (FPD). When the moisture content exceeded 280 ppm, FPD was reduced by 20%. The moisture content can be kept below this level by controlling moisture ingress with selected sealing gasket materials and by controlling the manufacturing conditions. The long-term stability and moisture penetration rate at 25°C and 60% relative humidity (RH) of the new HFA-227 formulation were tested over 36 months. Moisture content increased to approximately 210 ppm after 24 months and 230 ppm after 36 months storage; the drug content did not change over 24 months; FPD was slightly reduced by 24 months but still complied with the product specification. These results demonstrate that the critical moisture content of the Stmerin® D HFA-227 MDI formulation to meet required spray performance is between 280 and 330 ppm, and this formulation (at <210 ppm moisture level) is stable over 24 months.View full abstractDownload PDF (484K) -
Yukio Nohara, Junko Suzuki, Yoji Yamazaki, Hiroaki KuboArticle type: Regular Article
2012 Volume 60 Issue 5 Pages 598-602
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSIdebenone is a benzoquinone analog that is used in the treatment of several neurological disorders including Friedreich’s ataxia. It was found that the reaction of idebenone with 2-cyanoacetamide under alkaline conditions generates fluorescent products, and the reaction was considered to proceed via Craven’s reaction. The reaction mixture from idebenone gave fluorescence with excitation and emission maximum wavelengths at 358 nm and 409 nm, respectively. It was adopted for HPLC with post-column fluorescence derivatization of idebenone. Idebenone in the plasma showed a linear response in the range of 0.5–32 ng (25–1600 ng/mL), and the quantitation limit (S/N=10) was 12.5 ng/mL. The detection limit (S/N=3) of the standard solution of idebenone was 0.1 ng. The HPLC system was applied to the human blood plasma obtained by finger prick. The plasma sample obtained by finger prick gave a similar chromatogram to that of venous blood obtained by venipuncture.View full abstractDownload PDF (577K) -
John Rojas, Vijay KumarArticle type: Regular Article
2012 Volume 60 Issue 5 Pages 603-611
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSThe effect of silicification on the tableting performance of microcrystalline cellulose II (MCCII) was assessed through coprocessing with fumed silica via spray drying and wet granulation at the 98 : 2, 95 : 5, 90 : 10 and 80 : 20 ratios. Compacts produced by spray drying and wet granulation rendered better tensile strength than MCCII. The Kawakita and Heckel models implied that silicification increased compressibility and decreased the plastic deforming behavior and densification by die filling at the early stage of compression for MCCII. It also decreased the sensitivity to hydrophobic lubricants such as magnesium stearate, especially for the spray-dried products due to the competing effect with magnesium stearate. Further, silicification decreased the high elastic recovery typical of MCCII due to the increase in specific surface area and fragmenting behavior which contributed to the formation of stronger compacts. Moreover, silicification did not affect the fast disintegrating properties and release rates of poorly soluble drugs such as griseofulvin formulated in tablets compared to those of Prosolv® SMCC 50 and Prosolv® SMCC 90. The new silicified materials are appropriate to formulate fast disintegrating tablets by direct compression.View full abstractDownload PDF (3429K) -
Michiko Myose, Tsutomu Warashina, Toshio MiyaseArticle type: Regular Article
2012 Volume 60 Issue 5 Pages 612-623
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSThe MeOH extract of the seeds of Camellia sinensis (L.) KUNTZE gave twelve new saponins (1–12) along with ten known saponins (13–22). These saponins (1–22) showed stronger hyaluronidase inhibitory activity than the positive control, rosmarinic acid.View full abstractDownload PDF (633K) -
Yoshihisa Yamamoto, Toyofumi Suzuki, Mika Matsumoto, Michiteru Ohtani, ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 624-631
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSWe used near infrared (NIR) spectroscopy to evaluate the degree of mixing of blended dry syrup (DS) products whose particle sizes are not specified in the Revised 16th Edition of the Japanese Pharmacopoeia, and also evaluated the degree of mixing when powder products or fine granule products were added to DS products. The data obtained were used to investigate the relationship between the particle size distributions of the products studied and the degree of mixing. We found that the particle size distribution characteristics of the 15 DS products studied can be broadly classified into 5 types. Combinations of frequently prescribed products were selected to represent 4 of the 5 particle size distribution types and were blended with a mortar and pestle. The coefficient of variation (CV) decreased as the percent mass of Asverin® Dry Syrup 2% (Asverin-DS) increased in blends of Periactin® Powder 1% (Periactin) and Asverin-DS, indicating an improved degree of mixing (uniformity). In contrast, in blends of Periactin and Mucodyne® DS 33.3%, mixing a combination at a 1 : 1 mass ratio 40 times resulted in a CV of 20%. Other mixing frequencies and mass ratios resulted in a CV by 50% to 70%, indicating a very poor degree of mixing (poor uniformity). These results suggest that when combining different DSs, or a DS with a powder or fine granule product, the blending obtained with a mortar and pestle improves as the particle size distributions of the components approach each other and as the ranges of the distributions narrow.View full abstractDownload PDF (1972K) -
Hernán Pessoa-Mahana, Catalina Ugarte Núñez, Rami ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 632-638
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSA series of 3-[3-(4-aryl-1-piperazinyl)-propyl]-1H-indole derivatives (12a–h) was synthesized and evaluated for binding affinity at the human 5-hydroxytryptamine1A receptor (5-HT1AR) compounds (12b) and (12h) showed the highest 5-HT1A receptor affinity (IC50=15 nM). Molecular docking studies with all the compounds in a homology model of 5-HT1A showed that the main interaction anchoring the ligand in the receptor was a charge-reinforced bond between the protonated nitrogen atom (N-4) of the piperazine ring and Aspartate3.32.View full abstractDownload PDF (2653K) -
Tadatoshi Yamaguchi, Shigenobu Matsumoto, Toshiki Masumizu, Shinji Tak ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 639-646
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSThe various biological activity of dihydropyrazines(DHPs)due to the radical generation potency has been described in previous papers. Detailed data about radical species generating be mentioned here. The electron spin resonance (ESR) spin-trapping technique revealed that DHPs generate free radical species such as ·OH, ·OOH, ·CHR2 and ·CR3. Oxygen radicals and two carbon-centered radicals were detected as adducts of the spin traps DMPO and DBNBS, respectively. All the 5,5-dimethyl-1-pyrroline-N-oxide (DMPO)- and 3,5-dibromo-4-nitrosobenzenesulfonate (DBNBS)-adducts of compounds DHP-1–8 exhibited approximately the same signal patterns, with various levels of intensity depending on the substituent of the dihydropyrazine ring. The ESR signal intensity of DHPs also increased remarkably upon addition of Cu2+, resulting that the effects of DHPs were enhanced.View full abstractDownload PDF (1674K) -
Tatsuya Maruyama, Kenichi Onda, Takayuki Suzuki, Masahiko Hayakawa, Ta ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 647-658
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSIn the search for potent and selective human β3-adrenergic receptor (AR) agonists as potential drugs for use in treating obesity and non-insulin dependent (type 2) diabetes, a series of N-phenyl-(2-aminothiazol-4-yl)acetamides with phenoxypropanolamine moiety were prepared and their biological activities against human β3-, β2-, and β1-ARs were evaluated. Among these compounds, N-phenyl-(2-phenylaminothiazol-4-yl)acetamide (4g), N-phenyl-(2-benzylaminothiazol-4-yl)acetamide (4j), and N-phenyl-[2-(3-methoxyphenyl)aminothiazol-4-yl]acetamide (6g) derivatives showed potent agonistic activity against the β3-AR with functional selectivity over the β1- and β2-ARs. In addition, these compounds exhibited significant hypoglycemic activity in a rodent model of diabetes.View full abstractDownload PDF (1019K) -
Nan Jiang, Xin Zhai, Zhichao Chen, Chuang Liang, Chao Sun, Jing Han, P ...Article type: Regular Article
2012 Volume 60 Issue 5 Pages 659-664
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSWith an aim to develop promising anti-tumor agents, a novel series of 2-arylvinyl-4-aminoquinoline derivatives were designed, synthesized and evaluated for their cytotoxicity against H-460, HT-29, HepG2 and SGC-7901 cell lines in vitro. The pharmacological results indicated that most compounds were more potent than the positive controls, especially compounds 8, 14 and 16 with IC50 values ranging from 0.05 to 0.85 µM against all tested cell lines respectively, which were 5.7- to 112-fold better than Iressa. The most active compound 14 (IC50 values of 0.05, 0.25, 0.16, 0.68 µM), bearing 4-fluorostyryl at C-2 position and 3-(dimethylamino)-1-propylamino at C-4 position, showed great promise as a lead for the development of more effective quinoline analogues.View full abstractDownload PDF (708K)
Notes
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Yasutaka Otsuki, Akira Kotani, Fumiyo KusuArticle type: Note
2012 Volume 60 Issue 5 Pages 665-669
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSA capillary liquid chromatography with UV detection (CLC-UV) system has been developed for determining platinum-based antitumor drugs (e.g., cisplatin, carboplatin, and nedaplatin) in plasma based on the pre-column derivatization of platinum with N,N-diethyl dithiocarbamate (DDTC). The chelated platinum separation was carried out on a capillary column (Inertsil ODS-3, 150 mm×0.3 mm i.d., 3 µm) using an acetonitrile–water mixture (8 : 2, v/v) as a mobile phase that flowed at 5.0 µL/min. Detection was carried out by absorbance at 254 nm. Chromatographic peak height was found to be linearly related to the spiked concentration of nedaplatin in the blank control plasma from 5.0 ng/mL to 15 µg/mL (r2>0.998). The repeatability (n=5) of the chromatographic peak height for 2.5 µg/mL nedaplatin was 2.6% relative standard deviation (R.S.D.). The CLC-UV system, which required only 20 µL of plasma sample, was applied to the determination of total and free form platinum-based antitumor drugs in plasma after injection into rats. The recovery rates (n=5) of total and free form nedaplatin in plasma were 98% and 99%, respectively, and these repeatability were 2.4% R.S.D. and 3.1% R.S.D., respectively. In addition, the recovery rates (n=5) of total and free form carboplatin in plasma were 99% and 99%, respectively, and these repeatability were 2.9% R.S.D. and 0.24% R.S.D., respectively. The concentration–time profiles of total and free form nedaplatin in rat plasma were monitored to determine the pharmacokinetic parameters.View full abstractDownload PDF (443K) -
Ling-hua Zhu, Cheng Chen, Hui Wang, Wen-cai Ye, Guang-xiong ZhouArticle type: Note
2012 Volume 60 Issue 5 Pages 670-673
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSFive new indole alkaloids, alocasins A–E (3–7), together with known hyrtiosin B (1) and hyrtiosulawesin (2) were isolated from Alocasia macrorrhiza (L.) SCHOTT; their structures were elucidated on the basis of spectroscopic data. Compounds 1–7 were in vitro tested for cytostatic activity on human throat cancer (Hep-2), human hepatocarcinoma (Hep-G2), and human nasopharyngeal carcinoma epithelial (CNE) cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method; compounds 2, 3, 6 and 7 showed mild antiproliferative activity against Hep-2 and Hep-G2 whereas compounds 2 and 4 showed gentle antiproliferative activity against CNE.View full abstractDownload PDF (579K) -
Hisashi Matsuda, Makoto Hamao, Seikou Nakamura, Haruka Kon’i, Me ...Article type: Note
2012 Volume 60 Issue 5 Pages 674-680
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSEffects of principal saponins, chakasaponins I–III, from the flower buds of Camellia sinensis cultivated in Fujian province, China on plasma triglyceride (TG) and glucose levels in olive oil or sucrose-loaded mice were examined. Chakasaponins I–III at 50 and 100 mg/kg significantly inhibited increases in plasma TG and glucose levels. Furthermore, they prevented gastric emptying, suggesting that the former inhibitory effect is partly dependent on the inhibition of gastric emptying. In addition, the chemical structure of a new acylated oleanane-type triterpene oligoglycoside, chakasaponin IV, was elucidated on the basis of chemical and physicochemical evidence.View full abstractDownload PDF (607K) -
Masayuki Nasuda, Miho Ohmori, Kiyoshi Ohyama, Yoshinori FujimotoArticle type: Note
2012 Volume 60 Issue 5 Pages 681-685
Published: May 01, 2012
Released on J-STAGE: May 01, 2012
JOURNAL FREE ACCESSIn the past, we have questioned the accuracy of the stereochemistry of elisabethatriene, a putative biosynthetic intermediate of pseudopterosins, in light of the configuration of elisabethatrienol isolated from Pseudopterogorgia elisabethae, which was represented as 1S,4R,9S,11S. We have reinvestigated the stereochemistry of elisabethatriene. Elisabethatriene with the reported 1S,4R,9R,11S configuration was synthesized starting from (−)-isopulegol in its enantiomeric form. The 1H- and 13C-NMR data of the synthesized compound differed from those reported for elisabethatriene. In addition to the fact that elisabethatriene is converted into pseudopterosins, this finding has allowed us to propose that elisabethatriene should have the 1S,4R,9S,11S stereochemistry, which is identical to that of elisabethatrienol.View full abstractDownload PDF (618K)
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