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Volume 63, Issue 12
Displaying 1-15 of 15 articles from this issue
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Tatsushi Nakayama, Bunji Uno2015 Volume 63 Issue 12 Pages 967-973
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLThe superoxide O2·− scavenging reaction of (+)-catechin (Cat), quercetin (Que), rutin, and α-tocopherol (α-TOH) as natural phenolic compounds is investigated on the basis of electrochemical and ESR spectral measurements with the aid of density functional theory (DFT) calculations. Reversibility of the O2/O2·− redox couple is significantly affected by the presence of the phenolic compounds. The catechol moiety of Cat, Que, and rutin plays an essential role in concerted proton-coupled electron transfer (PCET) to HO2· derived from O2·− to give H2O2 and the corresponding o-benzoquinone radical anions. On the other hand, the presence of α-TOH causes sequential electron and proton transfers to HO2· to give H2O2 and the α-tocopheroxyl radical. These electron transfers in the presence of the phenolic compounds are inferred from the ESR spectral measurements. The DFT calculation results suggest that the O2·− scavenging reaction of the natural phenolic compounds proceeds efficiently with the one-step concerted PCET or sequential PCET mechanism.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1023K) Full view HTML -
Sudheer Moorkoth2015 Volume 63 Issue 12 Pages 974-985
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
Advance online publication: September 15, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLNovel heterocyclic analogs were synthesized by combining a flavone nucleus and thiazolidinone ring in an effort to potentiate the existing anti-cancer activity of flavone. The syntheses of 6-aminoflavone, 6-amino-3-methoxyflavone, 6-amino-3-methoxy-3′,4′-dimethxyflavone and their corresponding thiazolidinone analogs were performed. Fifteen novel analogs were synthesized and evaluated for their anti-cancer activity using cell-based assay techniques and in vivo testing. As expected, the analogs improved cytotoxicity and were shown to increase the life span of cancer-bearing mice. Cytotoxicity was evaluated using 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assays in HeLa, MDA-MB-435, and Vero cell lines. In vivo evaluation of anti-cancer activity performed in albino mice bearing Dalton’s ascites carcinoma showed that the new analogs enhanced life span and prevented increases in body weight owing to tumor volumes. Moreover, cell-cycle analysis and Hoechst staining analysis proved the apoptotic potential of these analogs. Preliminary pharmacokinetic evaluation was carried out on the synthesized compounds to determine the lipophilicity and pKa. Lipophilicity was determined using high-performance liquid chromatography and the results showed a direct correlation between the observed anti-cancer activity and log P value, while pKa values indicated the ionizing range which is a prediction tool for solubility and permeability.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1245K) Full view HTML -
Noriyuki Shino, Takahiro Uchida, Miyako Yoshida, Yasuo Nomura2015 Volume 63 Issue 12 Pages 986-991
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLA conventional nomogram, based on serum creatinine (sCr) and age, was developed in order to determine the correct initial dosage regimen for meropenem (MEPM) infusions in elderly patients with severe community-acquired pneumonia (CAP), using a target minimum inhibitory concentration (MIC) of 2 mg/L. A correlation between age and actual bodyweight (BW) in a development cohort of 44 males and 45 females was performed by linear regression using the least-squares method (male: y=−0.4676x+80.281, R2=0.4888; female: y=−0.4373x+77.502, R2=0.3194). There were no significant differences between actual BW and the BW (e-BW) estimated using this equation in this cohort (male: e-BW 41.6±3.1 kg, BW 41.7±3.5 kg, p=0.93; female: e-BW 39.5±2.1 kg, BW 39.5±3.7 kg, p=0.20). By integrating these equations using the Monte Carlo simulation method, a dosage regime was calculated which would have an 80% probability of maintaining plasma drug levels above the MIC for more than 40% of the time (>40%TAM), using only the age and sCr of individual patients. This relationship was summarized as a nomogram. The nomogram was validated using an independent validation cohort (n=28) of patients. An optimized dosage regimen could be predicted in 84 patients (94.4%) in the development cohort and 25 patients (89.3%) in the validation cohort. This nomogram may be a useful tool for clinicians and pharmacists in determining an initial MEPM regimen in elderly patients with severe CAP, based only on age and sCr.Graphical Abstract Fullsize ImageView full abstractDownload PDF (680K) Full view HTML -
Naoki Doi, Yasushi Sasai, Yukinori Yamauchi, Tetsuo Adachi, Masayuki K ...2015 Volume 63 Issue 12 Pages 992-997
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
Advance online publication: October 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLNovel polymeric prodrugs were synthesized by mechanochemical solid-state copolymerization of hydroxyethylcellulose and the methacryloyloxy derivative of 5-fluorouracil (5-FU). Copolymerization was about 94% complete after 4 h, and the polymeric prodrug was quantitatively obtained after 14 h of reaction. The number average molecular weight (Mn) and polydispersity (H) of the polymeric prodrug were 39000 g/mol and 6.20, respectively. Mechanical fracturing of the polymer in a stainless steel twin-shell blender improved these properties (Mn=16000 g/mol and H=1.94). 5-FU was sustainably released from the polymeric prodrugs, and the rate was not affected by the molecular weight or molecular weight distribution of the prodrug under the experimental conditions used. These results suggest that novel polymeric prodrugs composed of a polysaccharide and a synthetic polymer can be fabricated by mechanochemical solid-state copolymerization under anaerobic conditions.Graphical Abstract Fullsize ImageView full abstractDownload PDF (611K) Full view HTML -
Kazuya Otake, Satoru Azukizawa, Shigemitsu Takeda, Masaki Fukui, Arisa ...2015 Volume 63 Issue 12 Pages 998-1014
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLA novel series of 2,7-substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and biologically evaluated. (S)-2-(2-Furylacryloyl)-7-[2-(2-methylindane-2-yl)-5-methyloxazol-4-yl]methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylamine salt (13jE) was identified as a potent human peroxisome proliferator-activated receptor γ (PPARγ)-selective agonist (EC50=85 nM) and human protein–tyrosine phosphatase 1B (PTP-1B) inhibitor (IC50=1.0 µM). Compound 13jE partially activated PPARγ, but not PPARα or PPARδ, and antagonized farglitazar, a full PPARγ agonist. Cmax after the oral administration of 13jE at 10 mg/kg was 28.6 µg/mL (53 µM) in male Sprague-Dawley (SD) rats. Repeated administration of 13jE and rosiglitazone for 14 d at 10 mg/kg/d decreased plasma glucose and triglyceride levels significantly in male KK-Ay mice. Rosiglitazone, but not 13jE, significantly increased the plasma volume and liver weight. In conclusion, 13jE showed stronger hypoglycemic and hypolipidemic effects and weaker hemodilution and hepatotoxic effects than rosiglitazone, suggesting that its safer efficacy may be due to its partial PPARγ agonism and PTP-1B inhibition.Graphical Abstract Fullsize ImageView full abstractDownload PDF (1006K) Full view HTML -
Yasmine Mohamed Abdel Aziz, Mohamed Mokhtar Said, Hosam Ahmed El Shiha ...2015 Volume 63 Issue 12 Pages 1015-1028
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialA series of pyridothieno[3,2-d]pyrimidin-4-amines was designed and synthesized as congeners to the classical 4-anilinoquinazolines as ATP-competitive epidermal growth factor receptor (EGFR) inhibitors. Compound 5a exhibited the most potent and selective inhibitory activity against EGFR with an IC50 value of 36.7 nM. Moreover, compounds 4b and 5a showed remarkable cell growth inhibition against leukemia, central nervous system cancer, and non-small cell lung cancer cell lines that overexpress EGFR, with growth inhibition of 50% (GI50) values of around 10 nM in the full U.S. National Cancer Institute 60 cell panel assay. Cell cycle studies indicated that compounds 4b and 5a induced significant cell cycle arrest in the S-phase and G0/G1, respectively, in addition to boosting P27kip expression. Compound 5a did not alter the viability of placental trophoblasts, which reflects its safety for normal cells. The standard COMPARE analyses demonstrated considerable correlation levels between compounds 4b and 5a and erlotinib, with pyridinium chlorochromate (PCC) values of 0.707 and 0.727, respectively.Graphical Abstract Fullsize ImageView full abstractDownload PDF (2452K) Full view HTML -
Nahide Gülşah Deniz, Cemil Ibis, Zeliha Gokmen, Maryna Stasevych, Volo ...2015 Volume 63 Issue 12 Pages 1029-1039
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLIn the present paper, we report the synthesis, characterization, and biological evaluation as antifungal, antibacterial, antioxidant, and cytotoxic/anticancer agents of N-, S-, O-substituted-1,4-naphtho- and 2,5-bis(amino-substituted)-1,4-benzoquinone derivatives. In the synthesized compounds, antimicrobial activity at low concentrations against Escherichia coli B-906, Staphylococcus aureus 209-P, and Mycobacterium luteum B-917 bacteria and Candida tenuis VKM Y-70 and Aspergillus niger F-1119 fungi in comparison with controls was identified. 2-(N-Diphenylmethylpiperazin-1-yl)-3-chloro-1,4-naphthoquinone 9a was the most potent, with a minimum inhibitory concentration value of 3.9 µg/mL against test culture M. luteum. The synthesized compounds were screened for their antioxidant capacity using the cupric-reducing antioxidant capacity (CUPRAC) method. 2,2′-[1-(2-Aminoethyl)piperazin-1-yl]-3,3′-dichloro-bis(1,4-naphthoquinone) 10 showed the highest antioxidant capacity, with a 0.455 CUPRAC-trolox equivalent antioxidant capacity (TEAC) coefficient. Other parameters of antioxidant activity (scavenging effects on OH·, O2·－, and H2O2) of these compounds were also determined. The cytotoxic activity of the compounds was investigated by employing the sulforhodamine B cell viability assay against A549 (lung), MCF-7 (breast), DU145 (prostate), and HT-29 (colon) cancer cell lines. Compound 10 exhibited the most powerful cytotoxic activity at a concentration of 20 µM against all cell lines. In addition to the strongest antioxidant activity of compound 10, it also had lowest IC50 values (<3 µM), warranting further in vivo studies due to its anticancer activity.Graphical Abstract Fullsize ImageView full abstractDownload PDF (930K) Full view HTML -
Fumihiko Ogata, Naohito Kawasaki2015 Volume 63 Issue 12 Pages 1040-1046
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLMorphological and chemical evaluation of Fe–Mg hydrotalcite (Fe-HT) was performed using scanning electron microscopy, X-ray diffraction analysis, and electron microanalysis for application as an adsorbent for water treatment. The adsorption of arsenic III (As(III)) on Fe-HT was evaluated via examination of the effect of the contact time and analysis of the adsorption isotherm. The amount of As(III) adsorbed increased slightly with increasing temperature. The results of the adsorption isotherm studies suggested that As(III) adsorption can be well described by both the Freundlich and Langmuir equations. The adsorption of As(III) on Fe-HT reached equilibrium within 24 h, and the adsorption kinetic data fit the pseudo-second-order kinetic model better than the pseudo-first-order model. The amount of As(III) present on the surface of Fe-HT increased after As(III) adsorption, and the crystalline structure of Fe-HT was maintained after adsorption of As(III). The (003) and (006) peaks in the X-ray diffraction patterns were attributed to basal reflections, and these peaks shifted from respective 2θ values of 10.86 and 21.94° to 11.12 and 22.52°, indicating exchange of As(III) with chloride ions in Fe-HT with consequent narrowing of the inter-layer spacing. Collectively, these results suggest that Fe-HT is prospectively useful for the adsorption of As(III) from aqueous solutions.Graphical Abstract Fullsize ImageView full abstractDownload PDF (2028K) Full view HTML -
Susumu Kawakami, Katsuyoshi Matsunami, Hideaki Otsuka, Masanori Inagak ...2015 Volume 63 Issue 12 Pages 1047-1054
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLFrom the 1-BuOH-soluble fraction of a methanol (MeOH) extract of the leaves of Croton cascarilloides, crotofolanes: crotocascarins I–K, nor-crotofolane: crotocascarin γ, isocrotofolane glucoside and phenolic glycoside were isolated by a combination of various separation techniques. Their structures were elucidated mainly from the NMR spectroscopic evidence. The structure of crotocascarin K was first elucidated by spectroscopic analysis and then was confirmed by X-ray crystallographic analysis. Its absolute structure was finally determined by the modified Mosher’s method. Isocrotofolane glucoside was found to possess a new skeleton, however, its absolute structure remains to be determined.Graphical Abstract Fullsize ImageView full abstractDownload PDF (900K) Full view HTML -
Rasha Abdallah Azzam, Rafat Milad Mohareb2015 Volume 63 Issue 12 Pages 1055-1064
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLThe multi-component reaction of either acetoacetanilide derivative 1a or b with any of the aldehyde derivatives 2a–d and malononitrile 3 in the presence of triethylamine as a catalyst gave the 4H-pyran derivatives 4a–g, respectively. Carrying the same reaction but using a catalytic amount of ammonium acetate gave the 1,4-dihydropyridine derivatives 5a–f, respectively. The use of ethyl cyanoacetate instead of malononitrile in the presence of a catalytic amount of triethylamine gave the 4H-pyran derivatives 7a–d, respectively. Compound 4e was used to synthesize 1,4-dihydropyridine 9a–c and arylhydraone 11a–e derivatives were synthesized from 4a and e. The anti-tumor evaluations of the newly synthesized products were tested against six human cancer and normal cell lines. The results showed that compounds 4a, b, f, 5d, f, 9 and 11a–d had optimal cytotoxic effect against cancer cell lines with IC50<550 nM. The toxicity of the most active compounds was further measured against shrimp larvae.Graphical Abstract Fullsize ImageView full abstractDownload PDF (658K) Full view HTML
Notes
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Ae-Ran Choi, In-Kyoung Lee, E-Eum Woo, Jin-Won Kwon, Bong-Sik Yun, Hae ...2015 Volume 63 Issue 12 Pages 1065-1069
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialTwo new glabretal triterpenes, pancastatins A (1) and B (2), were isolated from the immature fruits of Poncirus trifoliata. Their chemical structures were elucidated by spectroscopic analyses including one- and two-dimensional NMR and high-resolution electrospray ionization mass spectrometry. Compounds 1 and 2 exhibited selective cytotoxicity against PANC-1 pancreatic cancer cells under low-glucose stress conditions.Graphical Abstract Fullsize ImageView full abstractDownload PDF (440K) Full view HTML -
Ryohei Mise, Yasunori Iwao, Shin-ichiro Kimura, Yukiko Osugi, Shuji No ...2015 Volume 63 Issue 12 Pages 1070-1075
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLThe effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100–200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.Graphical Abstract Fullsize ImageView full abstractDownload PDF (2909K) Full view HTML -
Yoon Kyung Kwon, Soo Jung Choi, Cho Rong Kim, Jae Kyeom Kim, Hye Kyung ...2015 Volume 63 Issue 12 Pages 1076-1080
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLThe aim of this study was to search for a novel choline acetyltransferase (ChAT) activator from plants traditionally grown in Korea. An ethanol extract from Chaenomeles sinensis Koehne showed the highest ChAT-activating effect in vitro in an assay that used human neuroblastoma cells and [14C]acetyl-CoA. The active compound was speculated to be stearic acid methyl ester (SAME). In an in vivo experiment, C. sinensis extract and SAME improved trimethyltin (TMT)-induced deficits in learning and memory in mice as assessed by a Y-maze behavioral test and a passive avoidance test. The C. sinensis extract might attenuate the TMT-induced brain disorder. This study suggests that SAME from C. sinensis might be useful in the treatment of Alzheimer’s disease.Graphical Abstract Fullsize ImageView full abstractDownload PDF (481K) Full view HTML -
Min Zhao, Shimiao Cheng, Weiping Yuan, Jianyong Dong, Kexin Huang, Zho ...2015 Volume 63 Issue 12 Pages 1081-1086
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
Advance online publication: September 17, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLFour new xenicanes, namely 4α-hydroxyisodictyohemiacetal (1), 4α-hydroxyisodictyoacetal (2), 13,18-diacetoxy-4-hydroxyisodictyo-19-al (3), and 4α-hydroxypachylactone (8), were isolated from a Chinese collection of the brown alga Dictyota plectens, along with four known analogues (4–7). The structures of the new diterpenes were determined by extensive spectroscopic data analysis. All compounds were evaluated for their antiviral activities against human immunodeficiency virus type 1 (HIV-1) and the highly pathogenic avian influenza A (H5N1) virus, and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages (PEMΦ).Graphical Abstract Fullsize ImageView full abstractDownload PDF (636K) Full view HTML -
Dan Zhao, Lijun Xie, Lei Yu, Ni An, Wei Na, Feng Chen, Youbin Li, Yinf ...2015 Volume 63 Issue 12 Pages 1087-1090
Published: December 01, 2015
Released on J-STAGE: December 01, 2015
JOURNAL FREE ACCESS FULL-TEXT HTMLFour new 2-benzoxazolinone-type alkaloids (acanthosides A–D) along with three known ones were isolated from the roots of Acanthus ilicifolius. Their structures were established by detailed interpretation of one dimensional (1D)- and two dimensional (2D)-NMR as well as high-resolution electrospray ionization (ESI)-MS data. The antiproliferative activities of these compounds were evaluated in vitro against three cultured cancer cell lines. The new compounds exhibited different levels of cytotoxicity against the HepG2, HeLa, and A-549 cancer cell lines with IC50 range 7.8–26.6 µM. In comparison with known compounds, the new isolates displayed better cytotoxic activities, which was attributable to the presence of substituted benzoyl moiety in their structures.Graphical Abstract Fullsize ImageView full abstractDownload PDF (389K) Full view HTML
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