Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 1-20 of 246 articles
  • Volume 70 (2022) Issue 5 Pages 309
    Foreword Read more
    Editor's pick

    The authors had held a symposium, “New modalities and strategies in drug delivery and discovery”, in the 36th Annual Meeting of the Academy of Pharmaceutical Science and Technology, Japan (APSTJ) in Tokushima (online), Japan, 2021. In the symposium, the active young researchers from the Graduate School of Biomedical Sciences of Tokushima University presented various topics on their own researches. This Current Topics accumulated the review articles from the invited speakers of the symposium. These reviews will provide a wide range of intimate information regarding new modalities and strategies in drug delivery and discovery.

  • Volume 70 (2022) Issue 5 Pages 362-368
    Monitoring and Predicting the Size of Fine Particles Prepared in a Fluidized-Bed Granulator Using a Handheld-Type Raman Spectrometer Read more
    Editor's pick

    Particle size-monitoring method using a handheld-type Raman spectrometer is proposed in this study. Two types of fine particles with the same formulation under different operating conditions were prepared for calibration purposes. There was a relationship between particle size and Raman intensity during processing and calibration curves could be obtained in both operating conditions. Two other types of fine particles with the same formulation, but on different scales or using different processing mechanisms were also prepared for verification purposes. The particle size could be successfully predicted using the calibration curve obtained taking powder porosity into consideration.

  • Volume 70 (2022) Issue 5 Pages 383-390
    Mechanism of Solubility Enhancement of Poorly Water-Soluble Drugs Triggered by Zeolitic Imidazolate Frameworks Read more
    Editor's pick

    The authors elucidated the mechanism of solubilization of poorly water-soluble drugs using zeolitic imidazolate frameworks (ZIFs), a member of metal-organic frameworks. The solubility of ZIF-trapped drugs was enhanced compared to the raw drugs. The authors focused on 2-methylimidazole (2-MIM), used as an organic ligand in ZIFs. Drugs were easily dissolved by the addition of 2-MIM, suggesting that the presence of 2-MIM enhanced the drug solubility. The findings of this study demonstrated the solubilization mechanism of poorly water-soluble drugs using ZIFs. ZIFs are expected to be used as drug carriers to maximize the bioavailability of poorly water-soluble drugs.

  • Volume 70 (2022) Issue 5 Pages 391-399
    Lipase-Catalyzed Kinetic Resolution of C1-Symmetric Heterocyclic Biaryls Read more
    Editor's pick

    The highly enantioselective lipase-catalyzed kinetic resolution (KR) of racemic C1-symmetric biaryl compounds including heterocyclic moieties, such as carbazole and dibenzofuran, has been achieved for the first time. This enzymatic esterification was accelerated by the addition of disodium carbonate while maintaining its high enantioselectivities (up to 99% ee), and was particularly effective for biaryls having N-substituted carbazole moieties. Furthermore, mesoporous silica-supported oxovanadium-catalyzed cross-dehydrogenative coupling of 3-hydroxycarbazole and 2-naphthol was followed by the lipase-catalyzed KR in one-pot to synthesize the optically active heterocyclic biaryl compounds with high optical purity.

  • Volume 70 (2022) Issue 4 Pages 245-253
    Formulation of Biopharmaceutical Dry Powder Inhaler Using the Void Forming Index (VFI) to Detect and Avoid Powder Caking in Dry Powder Inhaler Formulations Read more
    Editor's pick

    Biopharmaceutical dry powder inhaler (Bio-DPI) is an attractive formulation for non-invasive administration method for biopharmaceutical compounds. In Bio-DPI to ensure spray stability, it is important to control the powder caking risk of the formulation. To detect powder caking risk, Void Forming Index (VFI) is a useful method for DPI formulation study. The authors conducted formulation screening using VFI, to develop a high-dose Bio-DPI formulation containing 50 mg of lysozyme per capsule. As a result, VFI clarified the powder caking risk of each formulations and contributed to selection of high spray stability formulation.

  • Volume 70 (2022) Issue 4 Pages 261-268
    Synthesis and Evaluation of Habiterpenol Analogs Read more
    Editor's pick

    This paper describes the synthesis of new derivatives of habiterpenol and their structure-activity relationships. Habiterpenol is a G2 checkpoint inhibitor that has recently attracted attention as a new vital molecular-targeting therapeutic agent. Combination therapy using low-doses of anticancer agents and G2 checkpoint inhibitors has great potential as an effective treatment for cancer because it minimizes the dosage of the DNA-damaging anticancer agents and results in fewer side effects. The authors have independently developed a total synthesis to obtain new habiterpenol derivatives that cannot be derived from natural products, and have further studied their structure-activity relationships.

  • Volume 70 (2022) Issue 4 Pages 283-285
    Caulophyine A, a Rare Azapyrene Alkaloid from the Roots of Caulophyllum robustum Read more
    Editor's pick

    This paper reports one rare azapyrene alkaloid named caulophyine A along with six known compounds identified from the roots of Caulophyllum robustum Maxim., which was collected on Taibai mountain, the highest peak of the Qinling mountains, Shaanxi province, China. Caulophyine A is a nitrogen containing polycyclic aromatic hydrocarbon, possess a naphtho[2,1,8-def]isoquinoline fragment. This is the first report of the nitrogen containing azapyrene alkaloid identified from plant. The in vitro bioassays revealed that caulophyine A displayed weak acetylcholinesterase (AChE) inhibitory activity.

  • Volume 70 (2022) Issue 4 Pages 304-308
    Isolation of Natural Prodrug-Like Metabolite by Simulating Human Prodrug Activation in Filamentous Fungus Read more
    Editor's pick

    The authors successfully demonstrated that expression of a hCYP gene in a filamentous fungus led to the identification of a bioactive natural product from a strain previously not reported to produce the compound, and a prodrug-like secondary metabolite that can be activated by an hCYP. Our approach can be further developed by employing other types of CYPs and prodrug-activating enzymes in combination with microbes, with differing secondary metabolite biosynthetic potentials, to explore a wider biosynthetic space for identification of interesting prodrug-type natural products.

  • Volume 70 (2022) Issue 3 Pages 199-201
    Application of Acoustic Ejection MS System to High-Throughput Screening for SARS-CoV-2 3CL Protease Inhibitors Read more
    Editor's pick

    The application of mass spectrometry has been reevaluated in the field of pharmaceutical research. The recent launch of the EchoMS system, which combines an MS/MS system with an acoustic nano-liter dispensing system, has enabled label-free high-throughput screening (HTS) assays for disease-related enzyme reactions without time-consuming chromatographic separation. As the search for therapeutic agents for COVID-19 is currently underway, the authors conducted an HTS campaign for SARS-CoV-2 3CL protease using this system. A library of 32,033 compounds was assayed in 12 hours, and several inhibitors with antiviral activity were found in further cell-based assay.

  • Volume 70 (2022) Issue 3 Pages 211-219
    Synthesis and Characterization of Hydroxyethylamino- and Pyridyl-Substituted 2-Vinyl Chromone Derivatives for Detection of Cerebral Abnormal Prion Protein Deposits Read more
    Editor's pick

    Pathogenic scrapie PrP (PrPSc) accumulates in the brain resulting in the prion disease progression. SPECT imaging of PrPSc could non-invasively diagnose prion disease. The authors developed novel radioiodinated styryl chromone (SC) and vinyl pyridyl chromone (VPC) derivatives for PrPSc imaging. They found that the SC derivatives possess affinity for PrPSc, while the conversion to the VPC derivatives abolishes the affinity. These results indicate that a single aromatic ring in the imaging agents can make a significant difference in the recognition of PrPSc. [125I]SC-NHEtOH was shown to be a potential scaffold for the further development of prion imaging agents.

  • Volume 70 (2022) Issue 3 Pages 220-225
    Synthesis and Anti-dengue Virus Activity of 5-Ethynylimidazole-4-carboxamide (EICA) Nucleotide Prodrugs Read more
    Editor's pick

    Because 40% of the world’s population is faced with the risk of Dengue virus (DENV) infection and no drug has yet been approved, development of an anti-DENV agent is a key priority for human health. In this article, the authors revealed that a combination of 4’-thio-modification and introduction of monophosphate prodrug skeleton to nucleoside analog, for example 5-ethynyl-(1-b-D-ribofuranosyl)imidazole-4-carboxamide (EICAR), is valuable tactic to develop an effective anti-DENV agent.

  • Volume 70 (2022) Issue 3 Pages 235-239
    Synthesis of Visible-Light–Activated Hypervalent Iodine and Photo-oxidation under Visible Light Irradiation via a Direct S0→Tn Transition Read more
    Editor's pick

    The authors designed and synthesized two visible light-absorbing hypervalent iodines, and investigated their property of photo-reaction. Since heavy atom-containing molecules cause a direct triplet excitation, these molecules promoted photo-oxidation under the irradiation of wavelength exceeding their singlet excitation region. The various photo-oxidations are demonstrated: oxidation of primary and secondary alcohols, diol, and sulfoxide. Furthermore, spectroscopic analysis including phosphorescence excitation, and density functional theory calculations were performed to prove the reaction mechanism of the photo-oxidation in detail.

  • Volume 70 (2022) Issue 2 Pages 95-105
    Protein Chemical Modification Using Highly Reactive Species and Spatial Control of Catalytic Reactions Read more
    Editor's pick

    In this review, the author summarized his protein modification studies over the past decade. By utilizing highly reactive chemical species such as radical species and singlet oxygen, the author has developed novel methods for the selective modification of tyrosine and histidine residues, which have been difficult to be modified by conventional methods. In addition, The author took advantage of the high reactivity of these active species to apply protein modification reactions that proceed selectively in the space of a few nanometers around the catalyst.

  • Volume 70 (2022) Issue 2 Pages 130-137
    Surface Plasmon Resonance of Two-Dimensional Gold Colloidal Crystals Formed on Gold Plates Read more
    Editor's pick

    Surface plasmon resonance (SPR) sensors have been widely applied in various fields of biotechnology and pharmacology, including drug discovery, biomarker screening, virus detection, and food safety testing. In this report, a metal-insulator-metal (MIM) type SPR sensor was fabricated by placing an insulator layer on top of a gold thin film and then arranging gold colloidal particles in a two-dimensional regular array on the insulator layer. Because of resonance of the plasmons of the gold particles and the thin film, multiple plasmon peaks/dips were observed. The substrate was shown to have twice the sensing capability of the gold particles.

  • Volume 70 (2022) Issue 2 Pages 146-154
    Development of Scaled-Up Synthetic Method for Retinoid X Receptor Agonist NEt-3IB Contributing to Sustainable Development Goals Read more
    Editor's pick

    The United Nations’ Sustainable Development Goals (SDGs) provide guidelines for achieving a better and more sustainable future. Small-molecular drugs contribute to SDG3 (“Ensure healthy lives and promote well-being for all at all ages”), and waste reduction in small-molecular drug syntheses contributes to SDG6 (“Ensure availability and sustainable management of water and sanitation for all”) . The authors described an environmentally friendly scaled-up synthetic method for retinoid X receptor agonist NEt-3IB, a candidate for treating inflammatory bowel disease, by employing a reusable hydrophobic ether and ethanol.

  • Volume 70 (2022) Issue 2 Pages 155-161
    Chemical Synthesis and Evaluation of Exopolysaccharide Fragments Produced by Leuconostoc mesenteroides Strain NTM048 Read more
    Editor's pick

    Extracellular polysaccharides (EPSs) are carbohydrate polymers secreted by bacteria, fungi and algae, and have various biological activities. EPSs from Leuconostoc mesenteroides subsp. mesenteroides strain NTM048 (NTM048 EPS) enhance IgA production of mouse. In this study, the authors developed efficient synthetic routes to the NTM048 EPS fragments and evaluated their effects on IgA-inducing activity. The synthetic fragments showed a slight IgA-inducing activity, but the levels were not as high as those of the NTM048 EPS, revealing that the activity by EPS might be associated with the recognition of larger fragments or whole glucans, rather than the recognition of glycan substructures.

  • Volume 70 (2022) Issue 2 Pages 187-191
    Secorubenine, a Monoterpenoid Indole Alkaloid Glycoside from Adina rubescens: Isolation, Structure Elucidation, and Enantioselective Total Synthesis Read more
    Editor's pick

    The authors have isolated a new pentacyclic monoterpenoid indole alkaloid glycoside, named secorubenine, from the heartwood of Adina rubescens, a plant used as a traditional medicine in Southeast Asia. Its structure was determined by careful analysis of the collected NMR spectra and chemical modification of the isolated natural product. Furthermore, the enantioselective total synthesis of secorbenine was immediately achieved by applying the bioinspired total synthesis of monoterpenoid indole alkaloid glycosides previously established by the authors. Thus, the exact structure of secorubenine, including absolute stereochemistry, was confirmed.

  • Volume 70 (2022) Issue 1 Pages 1-9
    Elucidation of Complex Dynamic Intermolecular Interactions in Membranes Read more
    Editor's pick

    A combination of biophysical techniques revealed various complex molecular interactions in membranes.  Antimicrobial peptides form toroidal pores with surrounding lipids, followed by translocation into the cytosol.  Amyloid β-protein recognizes clusters of monosialoganglioside GM1 on neuronal membranes, forming toxic amyloid fibrils containing 2-residue-shifted antiparallel β-sheets.  The coiled–coil labeling method enables a quantitative analysis of membrane protein associations.  The introduction of a GXXXG motif drives the formation of an otherwise unfavorable parallel dimer of a model transmembrane helix.

  • Volume 70 (2022) Issue 1 Pages 10-11
    Foreword Read more
    Editor's pick

    These current topics introduce the latest research on the liquid chromatographic techniques utilized in food analysis. These liquid chromatographic techniques are based on various detection methods including UV detection, fluorescence detection, electrochemical detection and MS. These methods incorporate innovations that go beyond simple chromatography, such as derivatization to improve detectability of analyte, effective separation from matrices by fluorous chemistry, multidimensional chromatography to separate a wide range of polar compounds, and the use of methylated reference for the determination without calibration curves using single reference liquid chromatography. The contents of the topics would provide useful suggestions to improve analysis of important ingredients in food samples.

  • Volume 70 (2022) Issue 1 Pages 57-65
    Stabilizers for Osmium Isotopes in Microwave-Irradiated Acid Digestion and Inductively Coupled Plasma Mass Spectrometry Analysis Read more
    Editor's pick

    The overestimation of osmium is often observed in spike recovery test by ICP-MS. This is because osmium formed the highly volatile osmium tetroxide in an oxidation reaction when microwave digestion. The authors investigated the methods to stabilize osmium by using four compounds, thiourea, ascorbic acid, sodium sulfite, and potassium metabisulfite, that could reduce the overestimation of osmium isotopes. All compounds were useful for stabilizing osmium and showed good spike recovery results. The influence of adding compounds against other elements defined by Q3D was also investigated.