Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 101-100 of 255 articles
  • Volume 68 (2020) Issue 9 Pages 868-878
    Collaborative Study to Validate Purity Determination by 1H Quantitative NMR Spectroscopy by Using Internal Calibration Methodology Read more
    Editor's pick

    Quantitative nuclear magnetic resonance is a powerful tool in quantitative determination of the main component and impurities in a drug substance or a drug product because of its high accuracy, precision and efficiency. This method has the potential to establish metrological traceability easily and expected to be widely utilized for some compendial guidelines and official standards. In this study, the authors conducted an inter-laboratory comparison for qNMR methodology and confirmed that statistically qNMR has the competence to obtain the same quantification performance and accuracy as the conventional reliable methods.

  • Volume 68 (2020) Issue 9 Pages 885-890
    Labeling of Peroxide-Induced Oxidative Stress Hotspots by Hemin-Catalyzed Tyrosine Click Read more
    Editor's pick

    Tyrosyl radical generation plays a major role in hemin/peroxide-induced oxidative stress. The authors developed a method for trapping tyrosyl radicals using a derivative of N-methyl luminol, a tyrosine labeling reagent. The derivative selectively forms a covalent bond with tyrosine residue (tyrosine click reaction) under single-electron oxidation conditions. This reaction labels oxidative stress hotspots not only at the protein level but also at the level of tyrosine residues undergoing oxidation. The cover picture depicts an image of tyrosine click reaction to aid in the visualization of hemin/peroxide-induced oxidative stress generated in blood vessels.

  • Volume 68 (2020) Issue 8 Pages 683-693
    Development of Transition-Metal-Catalysed Cross-Coupling Reactions through Ammonium C–N Bond Cleavage Read more
    Editor's pick

    Amine groups occur widely in many naturally abundant chemicals and artificial functional molecules. Efficient C–N bond conversion methods suitable for late-stage functionalization would greatly expand their synthetic utility. However, transformation of C–N bond is generally difficult, due to the high stability. Ammonium salt is an ideal pre-activation form for amine, since it can be obtained quantitatively from amine via simple protocol. In this review, synthetic transformations through ammonium C–N bond cleavage developed by the author’s group are summarised, describing a new trend for utilization of amine in organic synthesis.

  • Volume 68 (2020) Issue 8 Pages 753-761
    Screening, Synthesis, and Evaluation of Novel Isoflavone Derivatives as Inhibitors of Human Golgi β-Galactosidase Read more
    Editor's pick

    The authors previously reported novel β-galactosidase activity in the human Golgi apparatus and predicted the precursor GLB1 isoform 1 as the enzyme responsible for this activity. GLB1 isoform 1 is involved in lysosomal storage diseases and widely used as a biomarker of cellular senescence. Inhibitor-derived chemical probes may serve as powerful tools for identifying the enzyme. In this study, the authors screened inhibitors from two compound libraries. One of the obtained inhibitors showed increased inhibitory activity following redesigning using molecular docking simulations. This inhibitor may be useful for developing chemical probes to identify the enzyme discovered by the authors.

  • Volume 68 (2020) Issue 8 Pages 762-765
    Simple and Rapid Evaluation of the Unique Manuka Factor in Manuka Honey Using Fluorescence Fingerprints and Principal Component Analysis Read more
    Editor's pick

    Honey produced from manuka in New Zealand has exceptionally high antibacterial activity and is approved as a medicine for wound care. In this paper, authors developed a simple and rapid evaluation method for the antibacterial activity of manuka honey by using a fluorescence fingerprint (excitation and emission matrix). Three distinct wavelength combinations of fluorescence were obtained from the honey samples. A correlation between the fingerprint and the antibacterial activity was indicated by a multivariate analysis, and authors succeeded in the evaluation of the activity from the fingerprint. Furthermore, some chemicals (leptosperin and leptosperin) were indicated as antibacterial compounds in the honey.

  • Volume 68 (2020) Issue 8 Pages 773-778
    Risk Prediction Method for Anticholinergic Action Using Auto-quantitative Structure–Activity Relationship and Docking Study with Molecular Operating Environment Read more
    Editor's pick

    There are a lot of medicines having anticholinergic actions as side effect. However, it is sometimes difficult to examine side effect only in clinical studies because of various limitations. Therefore, the authors tried to predict anticholinergic activity on the basis of compound’s structures by quantitative structure-activity relationship (QSAR) and docking study. These methods might be helpful for risk assessment of anticholinergic side effects.

  • Volume 68 (2020) Issue 8 Pages 791-796
    Robust Nanoparticle Morphology and Size Analysis by Atomic Force Microscopy for Standardization Read more
    Editor's pick

    Because of the complexity of nanomedicines, analysis of their morphology and size has attracted considerable attention. The atomic force microscope (AFM) has emerged as a powerful tool for providing detailed morphological characteristics of nanoparticles. To assess the applicability of standardization of AFM as an analytical methodology of nanomedicines, in this study, authors identified robust conditions for assessing the morphology and size of nanoparticles based on a polystyrene nanoparticle certified reference material standard. Under the optimized conditions, there were no significant inter-instrument differences in the analyzed size values of polystyrene nanoparticles both in air and under aqueous conditions.

  • Volume 68 (2020) Issue 7 Pages 560-566
    Bone-Targeted Drug Delivery Systems and Strategies for Treatment of Bone Metastasis Read more
    Editor's pick

    This paper analyzes and summarizes the development of novel drug formulations in order to optimize targeted drug delivery in the treatment of bone metastasis using bone-targeting ligands and antibodies to metastatic cancer. Metastases of the bone is a common development especially in patients with breast and prostate cancers. However, most drugs are inefficiently distributed to the bone and are hence pharmacologically suboptimal in treating metastases in the bone. This paper could be useful for the development of drug targeting technologies for the treatment of bone metastasis.

  • Volume 68 (2020) Issue 7 Pages 567-582
    Recent Strategies for Targeted Brain Drug Delivery Read more
    Editor's pick

    Because brain disorders such as glioma, Alzheimer’s disease and Parkinson’s disease are lethal, or cause severe symptoms, medical treatment is needed. Recently, with the progress of understanding pathology, new therapeutic candidates have been developed. However, there are still unmet medical needs in the medication of brain disorder. This is mainly because most drugs cannot cross blood-brain barrier (BBB). To solve this problem, drug delivery system (DDS) using some approaches (e.g. antibody, nanocarrier, ultrasound irradiation) is being studied for overcoming BBB. In this review, we comprehensively reviewed on the development and therapeutic application of brain-targeted DDS.

  • Volume 68 (2020) Issue 7 Pages 583-588
    Drug Delivery System for Refractory Cancer Therapy via an Endogenous Albumin Transport System Read more
    Editor's pick

    Passive targeting can be applied to a relatively wide range of cancer types due to the enhanced permeability and retention (EPR) effect that is the basis of its theory. However, recent clinical data indicate that the tumor accumulation is only approximately 10% of the dose, and satisfactory results are most rarely obtained using only EPR effect strategy. In this article, the authors introduce the strategy of enhancing the EPR effect using S-nitrosated human serum albumin dimer (SNO-HSA Dimer) and the DDS strategy utilizing the endogenous albumin transport (EAT) system of tumor cells and its future development.

  • Volume 68 (2020) Issue 7 Pages 589-602
    Present Situation and Future Progress of Inhaled Lung Cancer Therapy: Necessity of Inhaled Formulations with Drug Delivery Functions Read more
    Editor's pick

    Inhaled lung cancer therapy is promising because of direct and noninvasive drug delivery to the lungs with low potential for severe systemic toxicity. In all clinical trials with nebulization of chemotherapeutic drugs, however, there was no obviously superior anticancer efficacy in lung cancer patients even at the maximum doses of drugs limited by pulmonary toxicity. Thus the addition of further drug delivery functions including sustained release, prolonged retention, and targeting in the lungs has been strongly desired to achieve enhanced anticancer efficacy and attenuated pulmonary toxicity of inhaled chemotherapeutic drugs and other drug candidates.

  • Volume 68 (2020) Issue 7 Pages 603-612
    Co-delivery Systems of Multiple Drugs Using Nanotechnology for Future Cancer Therapy Read more
    Editor's pick

    Combination therapies using multiple drugs are the effective strategies to treat tumors. Various therapeutic regimens have been developed. Here, co-delivery of multiple drugs to tumor tissues using nanotechnology is theoretically useful to improve the efficacy and safety of the regimens. In this review, the authors summarized the current state of co-delivery systems of multiple drugs, including small-molecular chemotherapeutic drugs, proteins, nucleic acids and gene medicines. Especially, they pointed out the importance of selection of the combination, targeted delivery of multiple drugs, and controlled release of drugs based on environment-responsive mechanisms. Co-delivery systems are the promising approach even for immunotherapy using checkpoint inhibitors.

  • Volume 68 (2020) Issue 6 Pages 491-511
    Fluorofunctionalizations of C–C Multiple Bonds and C–H Bonds Read more
    Editor's pick

    Introduction of a fluorofunctional group into organic compounds has been an important topic in the pharmaceutical science field. Although various types of fluorofunctionalizations have been actively investigated so far, applicable substrates are still limited and the development of a new methodology for the preparation of new materials having fluorofunctional groups is in high demand. In this personal account, 1) trifluoromethylations of C–C multiple bonds, 2) asymmetric fluorofunctionalizations of alkenes, and 3) C–H fluorofunctionalizations, which have been reported by the author and co-workers, are described.

  • Volume 68 (2020) Issue 6 Pages 512-515
    Enzymatic Stability of Myostatin Inhibitory 16-mer Peptides Read more
    Editor's pick

    Myostatin is a negative regulator of skeletal muscle growth. Recently, the authors developed 16-mer peptidic myostatin inhibitor MIPE-1686, which enhances muscle mass and grip strength in mice. The present study demonstrates that a linear peptide MIPE-1686 with N-terminal unprotected is amazingly stable against recombinant human proteases (aminopeptidase N, etc.). This implies that MIPE-1686 has a potential to act long-lasting in vivo. The results also suggest that the secondary structure of a relatively small linear peptide may influence the recognition by degradation enzymes. This would give a valuable information for designing a stable linear peptide drug in vivo.

  • Volume 68 (2020) Issue 6 Pages 520-525
    Asymmetric Nitrogen-Containing Dimer from Aerial Parts of Mercurialis leiocarpa and Its Synthesis by Mimicking Generation Process through Radical Intermediates Read more
    Editor's pick

    One of the oldest dye plants, Mercurialis leiocarpa (Euphorbiaceae), had been used as a blue dye until indigo dye appeared in Japan. The constituents are expected the application as medicines. In this paper, the authors isolated a new nitrogen-containing asymmetric dimer, leiocarpanine A, from the aerial parts of this plant and described the chemical elucidation, the estimation of the generation process, and the concise synthesis by mimicking the generation process through radical intermediates. This synthetic method provides a rapid and concise pathway to construct a library of nitrogen-containing dimers that might be useful for drug discovery.

  • Volume 68 (2020) Issue 6 Pages 526-533
    Development of Specific Fluorogenic Substrates for Human β-N-Acetyl-D-hexosaminidase A for Cell-Based Assays Read more
    Editor's pick

    Inhibitors of human β-N-acetyl-D-hexosaminidase A, hHEXA, have the potential to a pharmacological chaperone for Sandhoff disease and Tay-Sachs disease as lysosomal storage diseases. The hHEXA inhibitors have been shown to successfully enhance hHEXA levels, leading to the chronic form of these diseases. To develop hHEXA inhibitors, authors analyzed the hHEXA active site structure and designed the specific hHEXA fluorogenic substrates based on the authors’ substrate design platform. The designed substrates were synthesized and these were exhibited excellent specificity and sensitivity for hHEXA in three human cell lines. These are all new substrates that can be utilized to screen hHEXA inhibitors in human cells.

  • Volume 68 (2020) Issue 6 Pages 534-537
    Development of Hydrophilic Polyacrylamide Gel-Based Condensing Reagents Comprised of Chlorotriazine Read more
    Editor's pick

    There is a great need for reagents that are environmentally benign, easy to handle, inexpensive, and safe in organic synthesis. In this context, the authors have developed hydrophilic polyacrylamide-gel based triazine-type condensing reagents, PAG-Trz-Cls, which were synthesized from inexpensive materials via radical polymerization. PAG-Trz-Cls are non-hygroscopic solid, high-loading, well-swollen in water and alcohol. Owing to these features, condensation between highly polar carboxylic acids and amines in an aqueous solvent successfully proceeded, and purification of the resulting amides can be readily carried out by filtration.

  • Volume 68 (2020) Issue 5 Pages 405-420
    Development of Copper-Catalyzed Chemoselective Reactions Read more
    Editor's pick

    “Soft” nature of copper catalysis enabled two types of chemoselective reactions. First, C-C bond forming reactions at an anomeric carbon of unprotected aldoses were developed by taking advantage of orthogonal reactivity between “soft” organocopper species and “hard” polar functional groups, free hydroxy groups. Second, preferential reaction between “soft” copper species and “soft” C-C multiple bonds enabled difunctionalization of the multiple bonds by controlling the reaction order of three reactive species. Well-controlled stereo- and/or regioselectivity of the reactions is another important feature of the copper catalysts.

  • Volume 68 (2020) Issue 5 Pages 436-442
    Constituents of the Fruiting Body of Poisonous Mushroom Omphalotus japonicus Read more
    Editor's pick

    Omphalotus japonicus (Tsukiyotake in japanese) is well-known as a poisonous mushroom in Japan. In this study, the authors isolated six new sesquiterpenes, four known sesquiterpenes and two known steroids from the fruiting body of O. japonicus with column chromatography, solid-phase extraction (SPE), and HPLC. The chemical structures were determined with NMR, MS and IR spectra. Relative configuration was determined with NOE correlations and absolute configuration was determined with ECD calculation. Three new compounds showed growth-restoring activity against mutant yeast via calcium-signal transduction.

  • Volume 68 (2020) Issue 5 Pages 452-465
    Novel Indirect AMP-Activated Protein Kinase Activators: Identification of a Second-Generation Clinical Candidate with Improved Physicochemical Properties and Reduced hERG Inhibitory Activity Read more
    Editor's pick

    This paper describes that the synthesis and evaluation of novel indirect adenosine monophosphate-activated protein kinase (AMPK) activators. The series of compounds selectively inhibited cell growth in several human breast cancer cell lines by activating AMPK. The back-up medicinal chemistry synthetic research on ASP4132, a previously reported clinical compound that acts as an indirect AMPK activator, led to the successful identification of 27b as a second-generation clinical candidate with promising profiles such as high aqueous solubility and less human Ether-a-go-go Related Gene (hERG) channel inhibitory activity.