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Volume 62, Issue 10
Displaying 1-14 of 14 articles from this issue
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Regular Articles
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Aida Baharuddin, Asfarina Amir Hassan, Rozana Othman, Yongtao Xu, Meil ...2014 Volume 62 Issue 10 Pages 947-955
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
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Supplementary materialIn the efforts to find an anti-viral treatment for dengue, a simple tryptophan fluorescence-screening assay aimed at identifying dengue domain III envelope (EIII) protein inhibitors was developed. Residue Trp391 of EIII was used as an intrinsic probe to monitor the change in fluorescence of the tryptophan residue upon binding to a peptide. The analysis was based on the electron excitation at 280 nm and fluorescence emission at 300–400 nm of EIII, followed by quenching of fluorescence in the presence of potential peptidic inhibitors coded DS36wt, DS36opt, DN58wt and DN58opt. The present study found that the fluorescence of the recombinant EIII was quenched following the binding of DS36opt, DN58wt and DN58opt in a concentration-dependent manner. Since the λmax for emission remained unchanged, the effect was not due to a change in the environment of the tryptophan side chain. In contrast, a minimal fluorescence-quenching effect of DS36wt at 20 and 40 µM suggested that the DS36wt does not have any binding ability to EIII. This was supported by a simple native-page gel retardation assay that showed a band shift of EIII domain when incubated with DS36opt, DN58wt and DN58opt but not with DS36wt. We thus developed a low-cost and convenient spectrophotometric binding assay for the analysis of EIII–peptide interactions in a drug screening application.View full abstractDownload PDF (1715K) Full view HTML -
Motoyuki Isoda, Kazuyuki Sato, Yoriko Tokura, Atsushi Tarui, Masaaki O ...2014 Volume 62 Issue 10 Pages 956-961
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLAn asymmetric reductive aldol-type reaction of α,β-unsaturated esters with carbonyl compounds using Rh catalyst and Et2Zn was investigated. A chiral zinc complex from α,β-unsaturated ester was easily generated as the key intermediate from Et2Zn and Wilkinson’s catalyst with diisopropyl L-(+)-tartrate to give a variety of enantioenriched β-hydroxy esters. The reaction was also applied to the intramolecular reductive aldol cyclization.View full abstractDownload PDF (585K) Full view HTML -
Katsunori Shinohara, Miki Yamashita, Wataru Uchida, Chie Okabe, Shinji ...2014 Volume 62 Issue 10 Pages 962-966
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
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Supplementary materialWe prepared polypseudorotaxanes (PPRXs) composed of cyclodextrin (CyD) and polyethylene glycol (PEG) inside microspheres (MSs) by an emulsifying process using polypropylene glycol (PPG) that shows temperature-dependent hydrophilicity changes; PPG is hydrophobic at high temperatures but hydrophilic at low temperatures. An aqueous solution of CyD and PEG was dispersed as droplets in PPG at 60°C then cooled to 0°C to allow water of droplets to transfer into PPG. On removal of water in the droplets, CyD and PEG were left behind as a CyD/PEG PPRX inside the solid-state MSs. Examination of α-, β-, and γ-CyD revealed that α-CyD was suitable for the formation of PPRX containing PEG in this MS preparation procedure. Interestingly, a new PPRX composed of α-CyD and PPG was formed in the α-CyD MSs when they were prepared in the absence of PEG from the aqueous solution of α-CyD. This MS fabrication procedure can control the size and shape of PPRX particles, and will contribute to the production of new types of CyD inclusion complexes.View full abstractDownload PDF (742K) Full view HTML -
Dian He, Jing Ma, Xiuxiao Shi, Chunyan Zhao, Meng Hou, Qingxin Guo, Sh ...2014 Volume 62 Issue 10 Pages 967-978
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
Advance online publication: July 18, 2014JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialWe aimed to design and synthesize novel γ-aminobutyric acid (GABA) derivatives with the combination of aspirin (ASA) of nerve rehabilitative pharmacophores so as to develop multifunctional drugs useful in the treatment of neurological disorders. Twenty-four novel esters and amides of 1a were synthesized, biologically evaluated for antiepileptic activity with the model of 4-aminopyridine (4-AP), and tested for their capacity of penetrating the blood–brain barrier (BBB) with HPLC. The distribution of 8a, ASA freed by 8a, 7c, and ASA freed by 7c within 24 h in brain tissue was measured. The structure–activity relationship (SAR) was established and the data of Computer Aided Drug Design (CADD) showed good results. With ED50 values of 0.3684–0.5199 mmol/kg, LD50 1.1487–1.3944 mmol/kg, and therapeutic index (TI) 2.65–3.15, compounds 8a, 3b, 4b, 6c, and 7c exhibited better antiepileptic activities in multiples of 0.3 to 2.2 against the control sodium valproate (VPA). Most importantly, 8a and 7c exhibited excellent antiepileptic activities with TI values of 3.15 and 3.12, respectively.View full abstractDownload PDF (876K) Full view HTML -
Akiyoshi Numadate, Yusuke Mita, Yotaro Matsumoto, Shinya Fujii, Yuichi ...2014 Volume 62 Issue 10 Pages 979-988
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLAn established inhibitor of dynamin-related protein 1 (Drp1), 3-(2,4-dichloro-5-methoxyphenyl)-2-thioxoquinazoline-4-one (mdivi-1), was recently reported also to show potent puromycin-sensitive aminopeptidase (PSA)-inhibitory activity. Herein, we report structural development of mdivi-1 derivatives and structure–activity relationship (SAR) analysis of the synthesized compounds, as well as the structurally related PSA-specific inhibitor 3-(2,6-diethylphenyl)quinazoline-2,4-dione (PAQ-22), with the aim of identifying key structural features for inhibitory activity in order to develop selective inhibitors of Drp1, which is a potential target for treatment of Huntington’s disease. Among the synthesized compounds, 3-(4-chloro-3-methoxyphenyl)-2-thioxoquinazoline-4-one (10g) exhibited more potent Drp1-inhibitory activity than mdivi-1 with high selectivity for Drp1 over PSA.View full abstractDownload PDF (703K) Full view HTML -
Yoshinori Onuki, Naoki Hasegawa, Mayumi Ikegami-Kawai, Takako Suematsu ...2014 Volume 62 Issue 10 Pages 989-993
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLThe crystallization of phenytoin occurring after its dilution with infusion fluid is a major concern in the clinical use of injectable phenytoin. To gain further understanding of the crystallization, this study assessed details of the involvement of glucose in this action. For sample preparation, phenytoin crystals were created by diluting the injectable phenytoin with infusion fluids with different glucose concentrations at different temperature, and then the characteristics of the crystallization (e.g., crystal size in the long direction, accumulated amount over 24 h, and crystallization rate constant) were measured. Results of the analysis of variance indicated that the glucose concentration and temperature had significant impacts on the crystallization. The mode of action of the glucose concentration was suggested to be different from that of the incubation temperature. This study also examined the molecular mobility of components (i.e., glucose, propylene glycol, phenytoin) in the admixtures using diffusion NMR techniques. The findings will provide valuable information for the clinical use of injectable phenytoin.View full abstractDownload PDF (727K) Full view HTML -
A Novel Selenadiazole Derivative Induces Apoptosis in Human Glioma Cells by Dephosphorylation of AKTYikai Zhang, Shanyuan Zheng, Sai-Ming Ngai, Wenjie Zheng, Jinying Li, ...2014 Volume 62 Issue 10 Pages 994-999
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLSelenadiazole derivatives are synthetic organoselenium compounds with improved anticancer activity and greater selectivity than inorganic selenium. In this study, 4-(benzo[c][1,2,5]selenadiazol-6-yl)-benzene-1,2-diamine (BSBD) was shown to induce time- and dose-dependent apoptosis in SWO-38 human glioma cells by accumulation of a sub-G1 cell population, DNA fragmentation, nuclear condensation, caspase activation and poly(ADP-ribose) polymerase (PARP) cleavage. Further mechanistic investigation showed that BSBD treatment induced dephosphorylation of AKT and DNA damage-mediated activation of p53, leading to extensive apoptosis through the mitochondrial pathway. Our findings suggest that BSBD represents a potential human glioma therapeutic.View full abstractDownload PDF (1773K) Full view HTML -
Jing Li, Hua Liu, Li-li Liu, Chao-nan Cai, Hong-xia Xin, Wei Liu2014 Volume 62 Issue 10 Pages 1000-1008
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
Advance online publication: August 05, 2014JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialIn this study a brinzolamide drug–resin ophthalmic thermosensitive in situ gelling system was developed and evaluated. Brinzolamide was combined with ion exchange resins to prolong the retention time of drugs in the eye and to reduce ocular and systemic side effects. Poloxamer F127 was used as gelling vehicle in combination with carbopol 934P, which acted as a viscosity-enhancing agent. They were prepared using the cold method. The optimized formulation exhibited a sol–gel transition at 33.2±1.1°C with pseudoplastic flow behavior. This formulation was stable and nonirritant to rabbit eyes. In vitro release studies demonstrated diffusion-controlled release of brinzolamide from the combined solutions over a period of 8 h. In vivo evaluation (the elimination of brinzolamide through tears and absorption of brinzolamide in aqueous humor) indicated that the solution combination was better able to retain the drug than commercial preparations. Thus this formulation is safe for ophthalmic use and significantly increases brinzolamide bioavailability in aqueous humor.View full abstractDownload PDF (1068K) Full view HTML
Notes
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Ze-Ming Zhang, Chun-Hua Wang, Xiao-Jie Zeng, Qiu Qiu, Wei Tang, Guo-Qi ...2014 Volume 62 Issue 10 Pages 1009-1012
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLTwo new sesquiterpenoids, pinnatifone A (1) and pinnatifone B (2), and two new lignans, pinnatifolin (3) and isopinnatifolin (4), along with six known lignans (5–10), were isolated from the roots of Syringa pinnatifolia. The structures of the new compounds were elucidated by extensive spectroscopic methods, including NMR, MS, UV, and IR spectra. The lignans were screened for their anti-oxidant activity (2,2-diphenyl-1-picrylhydrazyl (DPPH) assay). Most of them showed potent anti-oxidant activity, especially compound 5, whose potent anti-oxidant activity had an SC50 value higher than that of the positive control vitamin C.View full abstractDownload PDF (377K) Full view HTML -
Nabil Samy Mamdouh, Sachiko Sugimoto, Katsuyoshi Matsunami, Hideaki Ot ...2014 Volume 62 Issue 10 Pages 1013-1018
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
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Supplementary materialThree new compounds were isolated from a MeOH extract of the leaves of Syzygium samarangense, one new cyanogenic glucoside, taxiphyllin 6′-O-gallate (1), one new megastigmane glucoside, actinidioionoside 6′-O-gallate (2), and one new sulfated flavonoid rhamnoside, myricetrin 2″-O-sulfate (3), together with 14 known compounds, lupeol (4), demethoxymatteucinol (5), cryptostrobin (6), betulinic acid (7), β-sitosterol glucoside (8), 2R-prunasin (9), myrciaphenone A (10), 1-feruloyl-β-D-glucopyranoside (11), (3S,5R,6R,7E,9S)-3,5,6,9-tetrahydroxymegastigman-7-ene (12), guaijaverin (13), myricetin 4′-methyl ether 3-O-α-L-rhamnopyranoside (14), myricetrin (15), gallic acid (16) and actinidioionoside (17). The structures of the new compounds were determined through a combination of spectroscopic, HPLC and chemical analyses.View full abstractDownload PDF (645K) Full view HTML -
Nami Ohashi, Wataru Nomura, Natsuki Minato, Hirokazu Tamamura2014 Volume 62 Issue 10 Pages 1019-1025
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
Advance online publication: August 08, 2014JOURNAL FREE ACCESS FULL-TEXT HTMLProtein kinase C (PKC) is correlated with cell signaling pathways and also receives attention as a therapeutic target for cancer and Alzheimer-type dementia. The application of Förster/fluorescence resonance energy transfer (FRET) phenomena to detect binding between proteins and small molecules, for example, PKC and its ligands, underlies a fluorescence-based assay method suitable for high-throughput screening. To accelerate studies on PKC functions in processing signals using small molecules and the development of drugs that target PKC, novel methods for the assessment of the PKC binding affinity of compounds are necessary. We previously developed solvatochromic fluorophore-based methods for that assessment. In this study, a novel method for a FRET-based PKC binding assay was developed and is expected to overcome the limitations of solvatochromic fluorophores.View full abstractDownload PDF (922K) Full view HTML -
Seikou Nakamura, Fengming Xu, Kiyofumi Ninomiya, Souichi Nakashima, Yo ...2014 Volume 62 Issue 10 Pages 1026-1031
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLAn 80% aqueous acetone extract of Cassia auriculata leaves was found to show a protective effect on D-galactosamine-induced cytotoxicity in primary cultured mouse hepatocytes. From the 80% aqueous acetone extract, we isolated a new benzocoumarin glycoside, avaraoside I (1), and a new flavanol dimer, avaraol I (2), together with 29 known constituents. The structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. In addition, three isolated compounds, pseudosemiglabrin (15, 0.0011%), (2S)-7,4′-dihydroxyflavan(4β→8)-catechin (22, 0.00075%), and (2S)-7,4′-dihydroxyflavan(4β→8)-gallocatechin (23, 0.092%), displayed hepatoprotective effects equivalent to that of the hepatoprotective agent, silybin.View full abstractDownload PDF (622K) Full view HTML -
Nobuko Mibu, Kazumi Yokomizo, Airi Koga, Miyuki Honda, Kou Mizokami, H ...2014 Volume 62 Issue 10 Pages 1032-1040
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
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Supplementary materialWe describe the synthesis and results of biological evaluation of newly designed 2,4,6-trisubstituted symmetrical 1,3,5-triazine (TAZ) derivatives. Among the tested trisubstituted TAZ derivatives, some CS-symmetrical alkoxy-amino-substituted TAZ derivatives, including 7ggp and 6dpp, showed significant antiviral activity against herpes simplex virus type 1 (HSV-1). The compound with the highest level of antiviral activity was C3-symmetrical trialkoxy-TAZ derivative 4bbb, which showed a considerably high selectivity index (IC50/EC50=256.6). The structure–activity relationships for anti-HSV-1 activity of the tested 2,4,6-trisubstituted TAZ derivatives are also described.View full abstractDownload PDF (639K) Full view HTML -
Hidemasa Hikawa, Maiko Hamada, Yuka Uchida, Shoko Kikkawa, Yuusaku Yok ...2014 Volume 62 Issue 10 Pages 1041-1044
Published: October 01, 2014
Released on J-STAGE: October 01, 2014
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Supplementary materialA method for enantioselective desymmetrization of N-Ac and N-Boc-FTY720 by nonenzymatic asymmetric acylation was developed. Effective enantioselective monobenzoylation using benzoyl chloride in the presence of the tetraphenylbisoxazoline (L2)–CuCl2 complex gave the desired products 3a and 3b in 52–62% yield with 64% ee.View full abstractDownload PDF (418K) Full view HTML
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