Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Volume 65 , Issue 12
Showing 1-13 articles out of 13 articles from the selected issue
Review
  • Hidetoshi Arakawa
    2017 Volume 65 Issue 12 Pages 1099-1112
    Published: December 01, 2017
    Released: December 01, 2017
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    One important aspect of analytical chemistry research in the pharmaceutical sciences is the development of diagnostic and therapeutic analyses for disease, and the development of analytical methods for elucidating the causes of disease. I have been focusing on developing a highly sensitive method for measuring trace amounts of specific components in biological samples. This research can be roughly divided into three approaches: the use of immunoassays and DNA hybridization as methods utilizing specific affinities, the use of capillary electrophoresis as a highly sensitive and rapid separation method, and the use of chemiluminescence and bioluminescence reactions. The components being measured are compounds such as hormones, tumor markers, drugs, reactive oxygen species and genes in biological samples for the purpose of developing therapies for the prevention and treatment of diseases.

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    Editor’s picks

    Analytical methods for disease diagnosis require high sensitivity and specific methods. For neonatal mass screening of congenital metabolic disorders, a 3 mm diameter disc of dried filter paper blood obtained from one drop of newborn blood is used, and one disc contains about 4 μL of blood. Diagnosis is performed by measuring hormones and genes in this disc. In hormone analysis, chemiluminescent enzyme immunoassay was developed. In genetic analysis, pyrophosphate generated by PCR amplification reaction or DNA fragment as amplification product was analyzed by luciferase bioluminescence method and capillary electrophoresis, respectively. In addition, identification of reactive oxygen species generated from natural medicines and antianginal drugs and their physiological action mechanism are described.

Communication to the Editor
  • Kwang-su Park, Kyungha Yoo, Mi Kyoung Kim, Woong Jung, Yoon Kyung Choi ...
    2017 Volume 65 Issue 12 Pages 1113-1116
    Published: December 01, 2017
    Released: December 01, 2017
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    Development of a novel, tau-selective near-infrared fluorescence (NIRF) probe was attempted by combining the 3,5-dimethoxy-N,N-dimethylaniline-4-yl moiety with an α-cyanoacetophenone via hexatrienyl π-linker. In particular, for structure–activity relationship study of the α-cyanoacetophenones, a chlorine substituent was introduced to the aromatic ring to give a series of compounds (2a2d). Among those, compound 2c with meta-chloro aryl substituent was identified as a tau-selective NIRF probe: selectivity for tau over amyloid β (Aβ) and bovine serum albumin (BSA) was estimated to be 10.3 and 19.5 fold, respectively. The mechanism for tau-selectivity of 2c was found to be based on the specific recognition of the microenviroment of tau fibrils, which was endowed by its molecular rotor-like properties. The tau-selective NIRF probe 2c was also able to stain tau fibrils in tau-green fluorescent protein (GFP)-transgenic human neuroblastoma cells (SH-SY5Y cells).

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Regular Articles
  • Rafat Milad Mohareb, Nermeen Saeed Abbas, Rehab Ali Ibrahim
    2017 Volume 65 Issue 12 Pages 1117-1131
    Published: December 01, 2017
    Released: December 01, 2017
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    The reaction of cyclohexan-1,4-dione with elemental sulfur and any of the 2-cyano-N-arylacetamide derivatives 2a–c gave the 2-amino-4,5-dihydrobenzo[b]thiophen-6(7H)-one derivatives 3a–c to be used in some heterocyclization reactions. The multicomponent reactions of any of compounds 3a–c with aromatic aldehydes 6a–c and either of malononitrile or ethylcyanoacetate gave the 5,9-dihydro-4H-thieno[2,3-f]chromene derivatives 9a–r, respectively. The anti-proliferative evaluation of the newly synthesized compounds against the six cancer cell lines A549, HT-29, MKN-45, U87MG, SMMC-7721 and H460 showed that the nine compounds 3c, 5c, 9e, 9h, 9i, 9j, 9l, 9q, 11e and 13e with highest cytotoxcity. Toxicity of these compounds against shrimp larvae revealed that compounds 3c, 9j, 9q, and 13e showed no toxicity against the tested organisms. The c-Met kinase inhibition of the most potent compounds showed that compounds 9j, 9q, 10e, 12e and 13e have the highest activities. Compounds 9j, 9l, 9q and 11e showed high activity towards tyrosine kinases. Moreover, compounds 9j, 9q and 13e showed the highest inhibitor activity towards Pim-1 kinase.

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  • Herman Palacio, Felipe Otálvaro, Luis Fernando Giraldo, Gilles Ponchel ...
    2017 Volume 65 Issue 12 Pages 1132-1143
    Published: December 01, 2017
    Released: December 01, 2017
    [Advance publication] Released: October 12, 2017
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    Drug delivery represents one of the most important research fields within the pharmaceutical industry. Different strategies are reported every day in a dynamic search for carriers with the ability to transport drugs across the body, avoiding or decreasing toxic issues and improving therapeutic activity. One of the most interesting strategies currently under research is the development of drug delivery systems sensitive to different stimuli, due to the high potential attributed to the selective delivery of the payload. In this work, a stimuli-sensitive nanocarrier was built with a bifunctional acrylic polymer, linked by imine and disulfide bonds to thiolate chitosan, the latter being a biopolymer widely known in the field of tissue engineering and drug delivery by its biodegradability and biocompatibility. These polymer nanoparticles were exposed to different changes in pH and redox potential, which are environments commonly found inside cancer cells. The results proof the ability of the nanoparticles to keep the original structure when either changes in pH or redox potential were applied individually. However, when both stimuli were applied simultaneously, a disassembly of the nanoparticles was evident. These special characteristics make these nanoparticles suitable nanocarriers with potential for the selective delivery of anticancer drugs.

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  • Ko Morishita, Yoshimichi Shoji, Shunkichi Tanaka, Masaki Fukui, Yuma I ...
    2017 Volume 65 Issue 12 Pages 1144-1160
    Published: December 01, 2017
    Released: December 01, 2017
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    A novel series of benzoylsulfonamide derivatives were synthesized and biologically evaluated. Among them, 4-(biphenyl-4-ylmethylsulfanylmethyl)-N-(hexane-1-sulfonyl)benzamide (compound 18K) was identified as a protein tyrosine phosphatase 1B (PTP1B) inhibitor with potent and selective inhibitory activity against PTP1B (IC50=0.25 µM). Compound 18K functioned as a non-competitive inhibitor and bound to the allosteric site of PTP1B. It also showed high oral absorption in mice (the maximum drug concentration (Cmax)=45.5 µM at 30 mg/kg), rats (Cmax=53.6 µM at 30 mg/kg), and beagles (Cmax=37.8 µM at 10 mg/kg), and significantly reduced plasma glucose levels at 30 mg/kg/d (per os (p.o.)) for one week with no side effects in db/db mice. In conclusion, the substituted benzoylsulfonamide was shown to be a novel scaffold of a non-competitive and allosteric PTP1B inhibitor, and compound 18K has potential as an efficacious and safe anti-diabetic drug as well as a useful tool for investigations of the physiological and pathophysiological effects of allosteric PTP1B inhibition.

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    Editor’s picks

    A novel series of benzoylsulfonamide derivatives were synthesized and biologically evaluated. Among them, compound 18K was shown to inhibit protein tyrosine phosphatase 1B (PTP1B) activity potently and non-competitively (IC50=0.25 μM). Molecular dynamics simulation demonstrated that 18K binds to the allosteric site of PTP1B. Compound 18K showed high oral absorption in mice, rats, and beagles, and markedly reduced plasma glucose levels, TG levels, and HOMA values with no side effects at 30 mg/kg (p.o.) for one week in db/db mice. In conclusion, the substituted benzoylsulfonamide is a novel scaffold of non-competitive allosteric PTP1B inhibitors, and compound 18K is a promising candidate for an efficacious and safe anti-diabetic drug with anti-obesity effects.

  • Taiki Kohiki, Yusuke Nishikawa, Tsubasa Inokuma, Akira Shigenaga, Akir ...
    2017 Volume 65 Issue 12 Pages 1161-1166
    Published: December 01, 2017
    Released: December 01, 2017
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    A synthetic platform for chlorpromazine (CPZ) oligomers, which could be generated via photo-reaction of CPZ, is essential to promote their biological and structural studies. In this paper, the first synthetic platform for CPZ oligomers is described. A photo-irradiation experiment of CPZ to confirm whether the structure of the CPZ dimer generated by the photo-irradiation was identical to that prepared by our synthetic method is also reported.

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  • Chihiro Tsukano, Satoshi Suetsugu, Nobusuke Muto, Yoshiji Takemoto
    2017 Volume 65 Issue 12 Pages 1167-1174
    Published: December 01, 2017
    Released: December 01, 2017
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    Tetrahydrobiphenylene consists of cyclobutene fused with benzene and cyclohexene rings. In this paper, a direct method for synthesizing tetrahydrobiphenylenes based on a palladium (Pd)(0)-catalyzed C(sp2)–H functionalization was investigated. The developed method was applied to the synthesis of several tetrahydrobiphenylenes having an oxygen functionality at the ring juncture. The derivatization of a tetrahydrobiphenylene is also reported.

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    Editor’s picks

    This paper describes the development of a synthetic method for tetrahydrobiphenylenes and derivatives based on a palladium(0)-catalyzed C(sp2)−H functionalization. This is a new direct method for accessing partially hydrogenated biphenylenes. The derivatization of a tetrahydrobiphenylene is also reported.

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