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Volume 60, Issue 12
Displaying 1-17 of 17 articles from this issue
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Regular Articles
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Fei Liu, Yumei Zhao, Jianxu Sun, Yongliang Gao, Zhenqing ZhangArticle type: Regular Article
2012 Volume 60 Issue 12 Pages 1479-1486
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSThienorphine hydrochloride (ThH) is a highly insoluble and readily metabolized partial-opioid agonist. It is used for the treatment of pain and heroin addiction. This study aimed to formulate and evaluate sublingual delivery systems containing ThH. Dimethyl-β-cyclodextrin (DM-β-CD) can enhance the solubility and permeability of hydrophobic drugs. In this paper, ThH cyclodextrin inclusion complexes were prepared and administrated sublingually with the objective of improving the drug’s aqueous solubility, in vitro permeation rate, and in vivo absorption rate. The formulation was prepared with DM-β-CD using the freeze-dried method and characterized using phase solubility, differential scanning calorimetry (DSC), X-ray and NMR analyses. The results of each test indicated the formation of dynamic inclusion complexes between ThH and DM-β-CD. The inclusion complexes also showed significant increases in in vitro aqueous solubility and mucosal permeability. According to the pharmacokinetic study of the complex in rats, the AUC and Cmax values of the sublingual delivery group were 40 and 46 times higher than those of the gastrointestinal group, whereas tmax was shorter, which proved that in vivo absorption and metabolism had been improved. It can therefore be concluded that the inclusion technology and sublingual delivery system were suitable for ThH development.View full abstractDownload PDF (1161K) -
Jin Hisazumi, Tomoyuki Watanabe, Tatsuya Suzuki, Naoki Wakiyama, Katsu ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1487-1493
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSThe purpose of this research is to investigate the applicability of terahertz (THz) reflectance spectroscopy for quantification of drug substance in tablets, so as to demonstrate the feasibility for applying this technique to tableting process monitoring. In order to acquire a suitable absorbance spectrum for this purpose, it was necessary to enhance the reflection intensity. By using an aluminum plate as a mirror at the opposite surface of the tablet, a reasonable absorbance spectrum could be acquired to reflect the bulk information of the tablet. To assess the limit of tablet thickness, linearity between the tablet thickness and the absorbance value was investigated using lactose and mannitol tablets. Since linearity was found within 0.75–5.0 mm for both tablets using 0.4 and 0.8 THz region, it was confirmed that THz reflectance spectroscopy is applicable to tablets within at least 5.0 mm thickness. Mannitol tablets containing sodium salicylate as the model drug substance were used to investigate the quantitative performance of this technique. It was confirmed that the established calibration model was acceptable for this quantification because of the root-mean-squared error of cross-validation (RMSECV) being 1.95%. In order to evaluate the applicability of this technique, content quantitative performance in double layered tablets having active and placebo layers were assessed. Since this calibration model achieved the root-mean-squared error of prediction (RMSEP) of 1.42% for the double layered tablets, this technique was considered feasible even if the drug substance is localized in the tablets.View full abstractDownload PDF (1112K) -
Tran Hong Quang, Nguyen Thi Thanh Ngan, Chau Van Minh, Phan Van Kiem, ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1494-1501
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESS
Supplementary materialA novel withanolide glucoside, plantagiolide I (1), a new withanolide glucoside, plantagiolide J (2), and six known compounds (3–8) were isolated from the whole plant of Tacca plantaginea. Their structures were determined by spectroscopic and chemical methods. Compound 3 significantly inhibited tumor necrosis factor alpha (TNFα)-induced nuclear factor-kappaB (NF-κB) transcriptional activity in HepG2 cells in a dose-dependent manner, with IC50 values of 9.0 µM. Compounds 1–8 enhanced the transcriptional activity of peroxisome proliferator-activated receptors (PPARs) in a dose-dependent manner, with EC50 values ranging from 1.6 to 49.7 µM. In addition, the transactivational effects of compounds 1–8 on three individual PPAR subtypes, including PPARα, β(δ), and γ were evaluated. Compounds 1–8 significantly activated the transcriptional activity of PPARβ(δ), with EC50 values in a ranging from 4.1 to 29.6 µM. These results provide scientific support for the use of T. plantaginea and its components for the prevention and treatment of inflammatory and metabolic diseases.View full abstractDownload PDF (939K) -
Makoto Otsuka, Azusa Yamanaka, Tomohiro Uchino, Kuniko Otsuka, Kiyomi ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1502-1507
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
Advance online publication: September 25, 2012JOURNAL FREE ACCESSTo measure the rapid disintegration of Oral Disintegrating Tablets (ODT), a new test (XCT) was developed using X-ray computing tomography (X-ray CT). Placebo ODT, rapid disintegration candy (RDC) and Gaster®-D-Tablets (GAS) were used as model samples. All these ODTs were used to measure oral disintegration time (DT) in distilled water at 37±2°C by XCT. DTs were affected by the width of mesh screens, and degree to which the tablet holder vibrated from air bubbles. An in-vivo tablet disintegration test was performed for RDC using 11 volunteers. DT by the in-vivo method was significantly longer than that using the conventional tester. The experimental conditions for XCT such as the width of the mesh screen and degree of vibration were adjusted to be consistent with human DT values. Since DTs by the XCT method were almost the same as the human data, this method was able to quantitatively evaluate the rapid disintegration of ODT under the same conditions as inside the oral cavity. The DTs of four commercially available ODTs were comparatively evaluated by the XCT method, conventional tablet disintegration test and in-vivo method.View full abstractDownload PDF (1350K) -
Fang Miao, Xin-Juan Yang, Yan-Ni Ma, Feng Zheng, Xiao-Ping Song, Le Zh ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1508-1513
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
Advance online publication: September 21, 2012JOURNAL FREE ACCESSSanguinarine (1) and chelerythrine (2) are two quaternary benzo[c]phenanthridine alkaloids (QBAs). Eighteen derivatives of 1 and 2 were synthesized by modification of C=N+ bond and evaluated for their in vitro acaricidal activity against Psoroptes cuniculi, a mange mite. A new method was developed to prepare 6-alkoxy dihydro derivatives of 1 and 2 (1a–e, 2a–e). Among all the compounds, only 6-alkoxy dihydrosanguinarines (1a–e) showed significant acaricidal activity at 5.0 mg/mL and 1a possessed the strongest activity (50% lethal concentrations (LC50)=339.70±0.75 mg/L, 50% lethal time (LT50)=6.53±0.04 h), comparable with a standard drug ivermectin (LC50=168.19±11.79 mg/L, LT50=16.54±0.11 h). The iminium moiety in 1 and 2 was proven to be the determinant for their acaricidal properties. 6-Alkoxy dihydro derivatives (1a–e, 2a–e) were prodrugs of 1 and 2. Compared with 7,8-dimethoxy groups, 7,8-methylenedioxy group was able to significantly improve the bioactivity. The present results suggested that QBAs are promising candidates or lead compounds for the development of new isoquinoline acaricidal agents.View full abstractDownload PDF (515K) -
Qunyou Tan, Li Zhang, Liangke Zhang, Yongzhen Teng, Jingqing ZhangArticle type: Regular Article
2012 Volume 60 Issue 12 Pages 1514-1521
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSPyridostigmine bromide (PTB) is a highly soluble and extremely bitter drug. Here, an economic complexation technology combined with direct tablet compression method has been developed to meet the requirements of a patient friendly dosage known as taste-masked dispersible tablets loaded PTB (TPDPTs): (1) TPDPTs should have optimal disintegration and good physical resistance (hardness); (2) a low-cost, simple but practical preparation method suitable for industrial production is preferred from a cost perspective. Physicochemical properties of the inclusion complex of PTB with beta-cyclodextrin were investigated by Fourier transformed infrared spectroscopy, differential scanning calorimetry and UV spectroscopy. An orthogonal design was chosen to properly formulate TPDPTs. All volunteers regarded acceptable bitterness of TPDPTs. The properties including disintegration time, weight variation, friability, hardness, dispersible uniformity and drug content of TPDPTs were evaluated. The dissolution profile of TPDPTs in distilled water exhibited a fast rate. Pharmacokinetic results demonstrated that TPDPTs and the commercial tablets were bioequivalent.View full abstractDownload PDF (719K) -
Yuhzo Hieda, Tominari Choshi, Yoshinari Uchida, Haruto Fujioka, Sayuri ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1522-1530
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSTotal syntheses of (±)-carquinostatin A (1), and (R)-(−)-carquinostatin A (1a) together with its enantiomer, (S)-(+)-carquinostatin A (1b), possessing radical scavenging activity, were newly achieved. (±)-Carquinostatin A (1) was synthesized from 1-acetonyl-6-bromo-3-ethoxy-2-methylcarbazole (6), which was derived from the known 1-acetonyl-3-ethoxy-2-methylcarbazole (5). Introduction of a prenyl group at the 6-position of carbazole was successful in two steps. For the synthesis of (R)-(−)-carquinostatin A (1a) and (S)-(+)-carquinostatin A (1b), (R)-(−)-1-(2-acetoxypropyl)-3-hydroxy-2-methylcarbazole (15a) and (S)-(+)-3-hydroxy-1-(2-hydroxypropyl)-2-methylcarbazole (15b), prepared by lipase-QLM catalyzed enantioselective transesterification of 3-hydroxy-1-(2-hydroxypropyl)-2-methylcarbazole (14), were used as the chiral starting material.View full abstractDownload PDF (968K) -
Anil Kumar Mungara, Yong-Ki Park, Kap Duk LeeArticle type: Regular Article
2012 Volume 60 Issue 12 Pages 1531-1537
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
Advance online publication: September 14, 2012JOURNAL FREE ACCESSA novel series of carbazole-based α-aminophosphonates were synthesized by three component coupling of 6-bromo-9-ethyl-9H-carbazole-3-carbaldehyde, amine and diethyl phosphite using polyethylene glycol (PEG-400) as a green reaction media. The antiproliferative activity of these molecules was evaluated against three cancer cell lines. Of these, compounds 4c, 4e and 4m were found to exhibit good antiproliferative activity against three cancer cells, A549, MCF-7, and NCI-N87.View full abstractDownload PDF (643K) -
Khanitha Pudhom, Thanesuan Nuanyai, Kiminori MatsubaraArticle type: Regular Article
2012 Volume 60 Issue 12 Pages 1538-1543
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESS
Supplementary materialGardenia plants have long been used as traditional medicines in various countries including Thailand. In this study, two new 3,4-seco-cycloartane triterpenes, sootependial (1) and sootepenoic acid (2), were isolated from bud exudate of G. sootepensis, together with five known compounds. Their structures were elucidated on the basis of spectroscopic data. Sootependial (1) showed potent cytotoxicity selective to Hep-G2 cell lines and anti-angiogenic activity in ex vivo model (a rat aortic ring sprouting) assay. Furthermore, its angiogenic effect was found to occur mainly by suppressing endothelial cell proliferation and tubule formation, suggesting the potential of 1 as a lead compound for cancer treatment.View full abstractDownload PDF (952K) -
Tamer Zekry Attia, Taku Yamashita, Masayoshi Miyamoto, Atsushi Koizumi ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1544-1549
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
Advance online publication: September 27, 2012JOURNAL FREE ACCESSThe investigation of cytochrome P450 (CYP) mediated metabolism reactions by determination of enzyme kinetic parameters, Michaelis constant (Km), maximum reaction velocity (Vmax), and intrinsic clearance (CLint) is important aspects in discovery and development of drugs. The kinetic parameters can be used to predict the clearance prior to human administration and for better understanding the mechanism of clearance in vivo. In this study, the metabolic activities of three major hepatic CYP isoforms (2C19, 2D6, and 3A4) were investigated on structurally different central nervous system (CNS) acting drugs, amitriptyline, fluphenazine, and dothiepin. By using our novel in vitro evaluation system, we could compare the kinetic parameters for the metabolism of fluphenazine and dothiepin for the first time. Comparing CLint values thus obtained, we concluded that 2C19 could be predominant for metabolic activity on tricyclic antidepressants as expected, but not on phenothiazine-related antipsychotic drugs. Since the metabolism of CNS drugs is susceptible to single nucleotide polymorphisms of human gene, our results suggest that phenothiazine could be an alternative to clinical application of CNS drugs.View full abstractDownload PDF (871K) -
Yoshihide Usami, Ryo Watanabe, Yuiko Fujino, Makio Shibano, Chihiro Is ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1550-1560
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSThe divergent synthesis of natural withasomnines and analogues was achieved from 4-hydroxypyrazoles, which was prepared via alkaline hydrolysis of the Baeyer–Villiger oxidation products from 4-formylpyrazoles. Key steps of this synthesis are regioselective Claisen rearrangement of 4-allyloxypyrazoles and the Suzuki–Miyaura coupling of 5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl trifluoromethanesulfonate and commercially available arylboronic acids. The Suzuki–Miyaura coupling at the final step of this strategy enabled facile access to natural withasomnines and their analogues. The biological activities of the twelve synthesized compounds against cyclooxygenases-1 and -2 (COX-1 and COX-2) were evaluated.View full abstractDownload PDF (856K) -
Tsutomu Warashina, Kaoru Umehara, Toshio MiyaseArticle type: Regular Article
2012 Volume 60 Issue 12 Pages 1561-1573
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESS
Supplementary materialThe MeOH extract from dried whole Botrychium ternatum plants yielded 33 compounds, including seventeen new flavonoid glycosides and sixteen known compounds. The structures of new compounds were established using NMR spectroscopic analysis and chemical evidence.View full abstractDownload PDF (742K) -
Zhi-Bing Shi, Dan Zhao, Yan-Yan Huang, Yun Du, Xiang-Rong Cao, Zhu-Nan ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1574-1580
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESS
Supplementary materialThe signal transducer and activator of transcription 3 (STAT3) oncogene is a promising molecular target and its inhibitors have great potential as anticancer drugs. To identify novel and STAT3-selective inhibitors, a virtual screening based on Specs and Maybridge databases was conducted and a 6,6′-bibenzoxazole type small molecule, compound 3a with a inhibition constant Ki value of 494.32 nM to STAT3 was explored. Further, a novel series of derivatives originally derived from 3a was synthesized and evaluated through cell-based assays using human breast cancer cell lines, MDA-MB-468 and MCF-7 with or without constitutive expression of STAT3, respectively. In the series, 3a, 3c, 3d and 4e showed a better inhibitory activity with a good selectivity. Among them, 3a and 3c significantly inhibited STAT3 protein level and also displayed binding affinity for STAT3 that detected with flow injection analysis-quartz crystal microbalance (FIA-QCM) analysis system. The results provided a new lead for future design and development of potent STAT3 inhibitors.View full abstractDownload PDF (1514K) -
Nguyen Phuong Thao, Nguyen Hoai Nam, Nguyen Xuan Cuong, Tran Hong Quan ...Article type: Regular Article
2012 Volume 60 Issue 12 Pages 1581-1589
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESS
Supplementary materialNine new diterpenoids, termed sinumaximols A–I (1–3, 5–9, 12), together with three known compounds (4, 10, 11), were isolated from the methanol extract of the soft coral Sinularia maxima. Their structures were elucidated on the basis of extensive spectroscopic methods, including one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS). The isolated compounds were evaluated for their inhibitory effects on the lipopolysaccharide (LPS)-stimulated production of pro-inflammatory cytokines in bone marrow-derived dendritic cells (BMDCs). Among them, compounds 2, 3, and 11 were potent inhibitors of LPS-stimulated interleukin-12 (IL-12) p40 with half-maximal inhibitory concentration (IC50) values ranging from 4.35±0.12 to 18.04±0.21 µM. Compounds 2, 3, and 11 showed moderate inhibitory activity on IL-6 production with IC50 values ranging from 17.72±0.31 to 59.77±2.34 µM.View full abstractDownload PDF (934K)
Notes
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Eun La Kim, Jian Lin Li, Bin Xiao, Jongki Hong, Eun Sook Yoo, Won Duk ...Article type: Note
2012 Volume 60 Issue 12 Pages 1590-1593
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
Advance online publication: October 04, 2012JOURNAL FREE ACCESSA new cyclic tetrapeptide (1), along with known congeners (2, 3), was isolated from the fungus Phoma sp. derived from the giant jellyfish Nemopilema nomurai. The absolute configuration of 1 was determined using the modified Mosher’s method and Marfey’s method. Compound 1 displayed a weak suppressive effect on the production of nitric oxide (NO) in murine macrophage cells (RAW264.7) without notable cytotoxicity.View full abstractDownload PDF (663K) -
Ken-ichi Fujita, Kensuke Inoue, Teruhisa Tsuchimoto, Hiroyuki YasudaArticle type: Note
2012 Volume 60 Issue 12 Pages 1594-1598
Published: 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSOsO42− immobilized on a poly(benzyl ether) dendrimer with a tertiary nitrogen at its core position efficiently catalyzed the homogeneous dihydroxylation of olefins with a low level of osmium leaching. The dendritic osmium catalyst could be applied to the wide range of olefins. Furthermore, the dendritic osmium catalyst was recovered by reprecipitation and then reused up to five times.View full abstractDownload PDF (591K) -
Takaaki Kubota, Shinya Watase, Hiroya Mukai, Jane Fromont, Jun’i ...Article type: Note
2012 Volume 60 Issue 12 Pages 1599-1601
Published: December 01, 2012
Released on J-STAGE: December 01, 2012
JOURNAL FREE ACCESSFour new bromotyrosine alkaloids, tyrokeradines C–F (1–4), have been isolated from Okinawan marine sponges of the order Verongidae. The structures of 1–4 were elucidated on the basis of spectroscopic data. Tyrokeradines C (1) and D (2) are new bromotyrosine alkaloids possesing an imidazole ring, while tyrokeradines E (3) and F (4) are new bromotyrosine alkaloids possesing a cyano group.View full abstractDownload PDF (267K)
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