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Volume 62, Issue 9
Displaying 1-14 of 14 articles from this issue
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Review
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Masafumi Ueda2014 Volume 62 Issue 9 Pages 845-855
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLThe application of conjugated oxime ethers to the synthesis of complex chemical scaffolds using domino radical reactions has been described in detail. The triethylborane-mediated hydroxysulfenylation reaction allows for the regioselective construction of a carbon–sulfur bond and a carbon–oxygen bond in a single operation for the formation of β-hydroxy sulfides. This reaction proceeds via a radical pathway involving regioselective thiyl addition and the subsequent trapping of the resulting α-imino radical with O2, where the imino group enhances the stability of the intermediate radical. Hydroxyalkylation reactions that occur via a carbon radical addition reaction followed by the hydroxylation of the resulting N-borylenamine with O2 have also been developed. We investigated sequential radical addition aldol-type reactions in detail to explore the novel domino reactions that occur via the generation of N-borylenamine. The radical reaction of a conjugated oxime ether with triethylborane in the presence of an aldehyde affords γ-butyrolactone via sequential processes including ethyl radical addition, the generation of N-borylenamine, an aldol-type reaction with an aldehyde, and a lactonization reaction. A novel domino reaction has also been developed involving the [3,3]-sigmatropic rearrangement of N-boryl-N-phenoxyenamine. The triethylborane-mediated domino reactions of O-phenyl-conjugated oxime ethers afforded the corresponding benzofuro[2,3-b]pyrrol-2-ones via a radical addition/[3,3]-sigmatropic rearrangement/cyclization/lactamization cascade.View full abstractDownload PDF (1291K) Full view HTML
Regular Articles
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Hoda Ibrahim El Diwani, Heba Tawfik Abdel-Mohsen, Ismail Salama, Fatma ...2014 Volume 62 Issue 9 Pages 856-866
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLIn this study, synthesis and docking studies of a series of new benzimidazole derivatives linked to substituted pyrimidines either through the methylenethio linkage or its bioisosteric methylene amino bridge were carried out. All the synthesized compounds were evaluated for their hepatitis C virus (HCV) RNA replication-inhibitory activity. Compounds 4d, 4f, and 4h were found to be more potent than VX-950 (IC50/90 of 4d=0.123/0.321, 4f=0.145/0.345, 4h=0.129/0.432, VX-950=0.20/0.45 µM, respectively) and 6d (IC50/90=0.116/0.452 µM) displayed activity very similar to that of the standard. Compounds 4d, 4f, 4h, and 6d were potent HCV RNA replication inhibitors and are good drug candidates for further investigations.View full abstractDownload PDF (3878K) Full view HTML -
Ling-Yih Hsu, Chih-Ying Nien, Wei-Ming Huang, Shou-Che Hsu, Tsu-Chung ...2014 Volume 62 Issue 9 Pages 867-874
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLUV-induced matrix metalloproteinase (MMP) production is considered a cause of skin aging. In this study, a number of novel bis{4-[N,N-di-(carboxymethyl)amino]phenoxy}alkane derivatives were synthesized and evaluated as UVA-protective agents. These compounds significantly protected human dermal fibroblast (HDF) cells from UVA-induced cytotoxicity and inhibited MMP-1 activation and expression with potency comparable to desferoxamine (DFO). Promoter activity assay indicated that they inhibited MMP-1 expression at the transcriptional level. Further studies revealed that the mechanism of these compounds may include blockage of the UVA-induced activation of the p38/mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) pathways. Together, these results suggest that further development of these compounds may be of interest.View full abstractDownload PDF (891K) Full view HTML -
Roshan Pradhan, Yong-Il Kim, Jee-Heon Jeong, Han-Gon Choi, Chul Soon Y ...2014 Volume 62 Issue 9 Pages 875-882
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLDoxorubicin (DOX)-loaded water-in-oil-in-water (W/O/W) microemulsions were produced using a shirasu–porous–glass (SPG) membrane emulsification technique. Soybean oil was used as the oil phase; polyglycerol polyricinoleate (PGPR) or tetraglycerol polyricinoleate (TGPR) was used as the surfactant to stabilize the feed W/O emulsions, while Tween 20 was used in the external water phase to stabilize oil droplets containing water droplets. Increasing the feed pressure from 50 to 90 kPa increased the particle size of W/O/W emulsions, whereas it was decreased by increasing the agitator speed. The smallest particle sizes of multiple emulsions were obtained at the feed pressure of 50 kPa and agitator speed of 350 rpm. Under this set of conditions, the increase in the concentration of PGPR or TGPR showed a decrease in the particle size of DOX-loaded W/O/W emulsions. The optimized formulation comprising of 5% w/v PGPR and 3% w/v Tween 20 in the oil phase and external water phase, respectively, with 0.5% w/v of DOX had a particle size of 0.440±0.007 µm and polydispersity index of 0.220±0.087, which was supported by the transmission electron microscopy image. The formulations showed a sustained release profile in phosphate buffer solution (pH 7.4). The plasma concentrations of DOX after intravenous administration to rats were prolonged and gave approximately 17-fold higher area under the drug concentration–time curve (AUC) compared to free DOX solution. Thus, these results demonstrated that the SPG membrane emulsification technique could be used as a promising technique to prepare W/O/W microemulsions for delivering DOX with sustained release characteristics and better bioavailability.View full abstractDownload PDF (1151K) Full view HTML -
Yun Sang, Heyin Pei, Liang Ma, Li Huang, Caifeng Xie, Jinying Chen, Xi ...2014 Volume 62 Issue 9 Pages 883-891
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialTriglycerides are the main part of fats and half of the lipids in hepatocytes, and play an important role in metabolism as energy sources and transporters of dietary fat. In this study, 33 derivatives based on 3-methyl-5-phenylthieno[2,3-d]pyrimidine-2,4(1H,3H)-dione were synthesized and evaluated for their lipid-lowering activity. Among them, compound 1i was found to exhibit potent triglyceride-lowering potency in 3T3-L1 adipocytes which was comparable to that of the adenosine monophosphate-activated protein kinase (AMPK) agonist Acadesine (AIACR). Furthermore, oral administration of 1i at a dose of 50 mg kg−1 d−1 for 5 weeks could reduce the mean body weight and liver weight by 12.02% and 32.00%, respectively, and regulated serum levels of triglycerides in diet-induced obese mice. The results indicate that compound 1i is a potential small-molecule for the treatment of diet-induced obesity and related diseases.View full abstractDownload PDF (885K) Full view HTML -
Fumihiko Ogata, Yuka Iwata, Naohito Kawasaki2014 Volume 62 Issue 9 Pages 892-897
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLFly ash (FA) was hydrothermally treated in an alkaline solution to produce zeolite fly ash (Z-FA). The properties of the FA and Z-FA were investigated. The amounts of tungsten (W) adsorbed onto the FA and Z-FA surfaces were evaluated. Z-FA was produced by hydrothermally treating FA in an alkaline solution. The specific surface area and pore volume of the Z-FA were greater than those of the FA. More W was adsorbed onto the Z-FA surface than onto the FA surface. The adsorption isotherms for W were fitted using both the Freundlich and Langmuir equations. The equilibrium concentrations of W adsorbed onto the FA and Z-FA surfaces were subsequently reached within 20 h. The pseudo-second-order model more accurately described the data than did the pseudo-first-order model. Sodium hydroxide solutions (1–50 mmol/L) were used to easily recover W from Z-FA, indicating that Z-FA was useful for recovering W from aqueous solutions.View full abstractDownload PDF (488K) Full view HTML -
Feng Ren, Ying Zhong, Xi Mai, Yi Jing Liao, Chao Liu, Li Hua Feng, Wen ...2014 Volume 62 Issue 9 Pages 898-905
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLA series of novel benzyloxyurea derivatives was designed, synthesized by substituting different benzyls or phenyls on N,N′-positions of the hydroxyurea (HU). These target compounds were evaluated for their anticancer activity in vitro against human leukemia cell line K562 and murine leukemia cell line L1210 in comparison with HU by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Some of the compounds showed promising anticancer activity against the cells. Molecular docking experiments with Saccharomyces cerevisiae R1 domain indicated that 4a and 4f′ have stronger affinity than 4m and 4n. Flow cytometry study showed that compound 4g exerted greater apoptotic activity against K562 cells line than HU.View full abstractDownload PDF (3689K) Full view HTML -
Jinho Lee, Jongseong Park, Victor Sukbong Hong2014 Volume 62 Issue 9 Pages 906-914
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
Advance online publication: June 20, 2014JOURNAL FREE ACCESS FULL-TEXT HTMLPim kinases play a key role in the regulation of signaling pathways including proliferation, migration, and metabolism and are a potential target for cancer therapy. A series of 5-benzylidenethiazolidine-2,4-diones were synthesized as pim kinase inhibitors. The structure–activity relationships (SAR) of the analogues in inhibiting in vitro pim kinase activity as well as the proliferation of leukemia cell lines were examined. SAR studies indicated that a hydroxyl group at the 2-position of the benzene ring of 5-benzylidenethiazolidine-2,4-dione plays an important role in the inhibitory activity against all three pim kinases and replacement with a pyrazinyl group at the 5-position of the benzene ring of 5-benzylidenethiazolidine-2,4-dione improved activity significantly. The compounds exerted anti-proliferative activity against the three leukemia cell lines we tested. The most potent compound, 5i, had an EC50 value of 0.8 µM in the MV4-11 cell line. The result of kinase profiling indicated that compound 5i was highly selective for pim-kinases.View full abstractDownload PDF (753K) Full view HTML -
Chang Liu, Jia-Lian Tan, Si-Yu Xiao, Jie-Feng Liao, Guang-Rong Zou, Xi ...2014 Volume 62 Issue 9 Pages 915-920
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
Advance online publication: July 09, 2014JOURNAL FREE ACCESS FULL-TEXT HTML
Supplementary materialA series of novel potentially platelet aggregation-inhibiting 1,4-benzoxazine-3(4H)-one derivatives was designed and synthesized through Smiles rearrangement, reduction and acetylation reactions. The antiaggregatory activities of the target molecules on arterial blood samples from rabbits, expressed by IC50 values (μM), were then evaluated in vitro against ADP induced platelet aggregation. The favorable IC50 values of compound 8c (IC50=8.99 µM) and 8d (IC50=8.94 µM) indicated that these two compounds were the most potent molecules among all the synthesized compounds. A detailed molecular docking study to explore the interaction of compounds 8c and 8d with GP IIb/IIIa receptor showed that they these two compounds were docked into the active site of GPIIb/IIIa receptor. These results suggest that the 1,4-benzoxazine-3(4H)-one derivatives are promising lead compounds to develop new platelet aggregation inhibitors.View full abstractDownload PDF (2358K) Full view HTML -
Hideyuki Suzuki, Hideaki Muratake2014 Volume 62 Issue 9 Pages 921-926
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
Advance online publication: July 10, 2014JOURNAL FREE ACCESS FULL-TEXT HTMLWe synthesized oxatriquinane hexafluorophosphate bearing an ethoxycarbonylmethyl group 7 or a 2-oxopropyl group 11. Both of these organic oxonium cation compounds were obtained as stable solids. However, 1H-NMR analysis showed that oxatriquinane 7 was present as the oxonium cation in aprotic solvent CD3CN, but was in rapid equilibrium with ring-opened bicyclic compound 8 in protic solvent CD3OD. The oxatriquinane 11 also showed similar behavior in protic solvent. Phenyl-substituted oxatriquinanes 12 and 14 were also obtained as stable solids, and showed similar properties to 7 and 11.View full abstractDownload PDF (558K) Full view HTML -
Tetsuya Miyoshi, Norihiko Takeda, Masaki Fukami, Shohei Sato, Masafumi ...2014 Volume 62 Issue 9 Pages 927-932
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLA new method has been developed for the umpolung α-heteroarylation of ketones via an N-alkoxyenamine. The treatment of ketones with tris(heteroaryl)aluminum reagents in the presence of isoxazolidine gave the corresponding α-heteroarylated ketones in moderate to good yields.View full abstractDownload PDF (570K) Full view HTML
Notes
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Herman Odens, Todd Lowther, Steven Kridel, Laura Watts, Lauren Filippo ...2014 Volume 62 Issue 9 Pages 933-936
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLFatty acid synthase (FASN) is the enzyme that synthesizes fatty acids de novo in human cells. Although FASN is generally expressed at low levels in most normal tissues, its expression is highly upregulated in many cancers. Consistent with this notion, inhibition of FASN activity has demonstrated potential to halt proliferation and induce cell death in vitro and to block tumor growth in vivo. Consequently, FASN is widely recognized as a valuable therapeutic target. In this report, we describe a variety of 1,4-quinones and 9,10-anthraquinones, including several natural compounds and some newly synthesized compounds, that potently inhibit the thioesterase (TE) domain of FASN. Inhibition of recombinant TE activity, inhibition of cellular FASN, and cytotoxicity in human prostate cancer cell lines and normal fibroblasts, is shown for the most potent inhibitors. Collectively, the data illustrate the novel inhibitory capacity of the 1,4-quinone and 9,10-anthraquinone pharmacophores against FASN.View full abstractDownload PDF (476K) Full view HTML -
Marie Shimada, Masaaki Ozawa, Kojiro Iwamoto, Yoshiyasu Fukuyama, Akio ...2014 Volume 62 Issue 9 Pages 937-941
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
JOURNAL FREE ACCESS FULL-TEXT HTMLKiusianins A–D (1–4) were isolated from the leaves of a Japanese endemic plant, Tilia kiusiana, together with 14 known compounds. The structures of a new lanostane-type triterpenoid 1 and three new cholestane-type sterols 2–4 were elucidated by spectroscopic methods, including two dimensional (2D) NMR. All the compounds isolated were evaluated for their cytotoxicity against two human cancer cell lines, HeLa and HL-60.View full abstractDownload PDF (875K) Full view HTML -
Xiao Hu, Qi-Wen Xia, Yang-Yang Zhao, Qiu-Hong Zheng, Qin-Ying Liu, Li ...2014 Volume 62 Issue 9 Pages 942-946
Published: September 01, 2014
Released on J-STAGE: September 01, 2014
Advance online publication: June 26, 2014JOURNAL FREE ACCESS FULL-TEXT HTMLA rare hexacyclic oxindole alkaloid, speradine F (1), together with two novel tetracyclic oxindole alkaloids, speradines G (2) and H (3), were isolated from the marine-derived fungus Aspergillus oryzae. Their structures were determined by spectroscopic methods and X-ray diffraction analysis. This study is the first report on cyclopiazonic acid (CPA)-type alkaloids with a hexacyclic skeleton.View full abstractDownload PDF (762K) Full view HTML
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