Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 81-80 of 249 articles
  • Volume 68 (2020) Issue 12 Pages 1210-1219
    Synthesis of Nucleoside Derivatives of N-Acetyl-7-nitroindoline, Their Incorporation into the DNA Oligomer, and Evaluation of Their Photoreactivity in the DNA/RNA Duplex Read more
    Editor's pick

    Stimulus-responsive molecules that modify nucleic acids in a site- and base-selective manner play an important role for genomic research. N-Acetyl-7-nitroindoline is a characteristic in that its acetyl group is photo-activated to acetylate amines to form amides. In this study, the N-acetyl-7-nitroindoline part was connected to the 2´-deoxyribose part, which was incorporated into the oligodeoxynucleotide probes, and their photo-reactivities toward the complementary RNA were investigated. One probe was photo-activated to deacetylate to the nitroso derivative. Photo-activation of another probe induced acetylation of the RNA. An interesting finding was the cross-link formation of another probe with the RNA strand.

  • Volume 68 (2020) Issue 12 Pages 1220-1225
    Development of Nitrolactonization Mediated by Iron(III) Nitrate Nonahydrate Read more
    Editor's pick

    Nitrogen dioxide has been used as an oxidant and nitrating reagent in organic synthesis. However, its use is limited because it is harmful and hard to handle. Iron(III) nitrate nonahydrate has attracted attention as a source of nitrogen dioxide because it is a readily available reagent of low toxicity and cost. This paper describes development of nitrolactonization mediated by iron nitrate as a source of nitrogen dioxide. Nitrolactones obtained by this reaction could lead to useful compounds, such as 1,2-aminoalcohol and amino acid derivatives bearing a tetrasubstituted carbon center.

  • Volume 68 (2020) Issue 12 Pages 1226-1232
    Sequence-Independent Traceless Method for Preparation of Peptide/Protein Thioesters Using CPaseY-Mediated Hydrazinolysis Read more
    Editor's pick

    Peptide/protein thioesters function as an indispensable synthetic intermediate in Native Chemical Ligation (NCL) that has enjoyed great success in the chemical synthesis of proteins. Facile conversion of recombinant proteins to thioesters allows for the straightforward access to semi-synthetic proteins with chemically synthesized peptides used as an NCL partner. In this paper, the authors developed an efficient thioester-producing protocol. The protocol features the traceless conversion of the CysPro triple repeat–Leu-OH-tagged sequence to the corresponding thioesters by treatment with carboxypeptidase Y in the presence of hydrazine followed by an auto-processing of the CysPro units.

  • Volume 68 (2020) Issue 11 Pages 1013-1024
    Effect of the Molecularly Imprinted Polymer Component Ratio on Analytical Performance Read more
    Editor's pick

    Molecular imprinting has been broadly perceived as the most advanced technology for preparing various materials that have a specific recognition site with selective adsorption. MIPs (Molecular Imprinted Polymer) are three-dimensional polymers with specific recognition sites for a certain molecule. A MIP is formed by crosslinking template with monomers to create copolymers. For every MIP, each template:monomer:crosslinker ratio shows a distinct performance for a specific analyte. Ratio effect on analytical performances are briefly outlined in this review. From all reports in this review, the synthesis of MIP using a template:monomer:crosslinker ratio of 1:4:20 is more likely to provide optimal imprinting efficiency.

  • Volume 68 (2020) Issue 11 Pages 1034-1048
    Development of a Logic Model for Promoting Incorporation of the Concepts of Impurity-Related ICH Guidelines into Pharmacopoeias Based on Cause and Effect Analysis Read more
    Editor's pick

    With the globalization of the drug supply chain, the quality assurance of drugs is required worldwide. Pharmacopoeias provide public standards for the drug quality assurance, and smooth incorporation of the concepts of the international guidelines into pharmacopoeias is desired. In particular, impurities in drugs are to be controlled to ensure patient safety. The authors focused on the harmonized guidelines for residual solvents, elemental impurities, and mutagenic impurities, and proposed an approach for promoting incorporation of the concepts of the guidelines into pharmacopoeias by combining the cause and effect analysis and the logic model.

  • Volume 68 (2020) Issue 11 Pages 1055-1060
    Effect of Disintegrants on Prolongation of Tablet Disintegration Induced by Immersion in Xanthan Gum-Containing Thickening Solution: Contribution of Disintegrant Interactions with Disintegration Fluids Read more
    Editor's pick

    In clinical practice, a thickening solution is frequently used to allow easy swallowing of tablets as well as foods by patients suffering from dysphagia. This study investigated the effect of thickening solution on tablet disintegration. Model tablets containing different disintegrants were prepared and their disintegration times were measured. The tablet disintegration times were significantly prolonged by immersion in thickening solution containing xanthan gum and the degree of prolongation differed depending on the type of disintegrant contained in the tablets. These findings provide valuable information for design of tablet formulation and clinical medication management for older patients with dysphagia.

  • Volume 68 (2020) Issue 11 Pages 1074-1081
    Fragment-Based Discovery of Irreversible Covalent Inhibitors of Cysteine Proteases Using Chlorofluoroacetamide Library Read more
    Editor's pick

    Chlorofluoroacetamide (CFA) shows chemically tuned mild reactivity that is suitable as an electrophilic warhead for highly target selective covalent inhibitors. Assembly of a small set of CFA-appended fragment library and its screening against cysteine protease papain demonstrated the potential utility of CFA in novel covalent drug discovery using a fragment-based approach.

  • Volume 68 (2020) Issue 10 Pages 907-945
    Development of New Innovative Synthetic Organic Chemistry Using Lone Pairs of Oxygen Atoms Read more
    Editor's pick

    This review describes development of innovative reactions utilizing the characteristic reactivity of oxygen atoms, 1) asymmetric synthesis of chiral quaternary carbon centers, 2) asymmetric synthesis using acetal functions, and 3) organic chemistry using acetal-type reactive salt chemical species, and their application to the asymmetric synthesis of natural products such as Fredericamycin A, anthracycline antibiotics, scyphostatin, Sch 642305, stenin, claboronin, rubrenolide, rubrynolide, centrolobine, and decytospolides A and B, etc. In particular, reactions using acetal-type reactive salt chemical species can alter the retrosynthesis planned based on conventional reactions because they allow the coexistence of functional groups that normally cannot coexist.

  • Volume 68 (2020) Issue 10 Pages 954-961
    Binding Assays Using a Benzofurazan-Labeled Fluorescent Probe for Estrogen Receptor–Ligand Interactions Read more
    Editor's pick

    Binding assays are widely used to study the estrogenic activity of endocrine-disrupting chemicals targeting the estrogen receptor (ER). In this study, the authors synthesized benzofurazan-labeled estradiol (BD-E2) derivatives as a fluorescent ligand for ER binding assays. BD-E2 compounds exhibit spectroscopic properties with high fluorescence intensities and large Stokes shifts in a hydrophobic environment. Analysis of the fluorescent ligands and human recombinant ER interactions revealed that the fluorescence intensity increased in hydrophobic environments, such as the receptor-binding site. By evaluation of the bound ligands based on changes in the fluorescence intensity, the authors established a simple, rapid, reliable ER binding assay.

  • Volume 68 (2020) Issue 10 Pages 989-995
    Evaluation of Dantrolene Granules Extemporaneously Reformulated from Capsules in a Pharmacy Read more
    Editor's pick

    An extemporaneous preparation, sodium dantrolene granules, has been manufactured using planetary centrifugal granulation method in the pharmacy. The amount of water was determined based on plastic limit value of the formulation, which is a critical parameter of the granulation method. The granulation process completes within 45 s, followed by coating process (20 s). The resultant granules show sharp particle size distribution and excellent flowability. The bulky powder was reformulated to the granules with non-adhesive and free-flowing properties. Thus, the granulation improves the usability of the medicine in the dispensing and dosing processes.

  • Volume 68 (2020) Issue 10 Pages 1001-1007
    Nitrate Ion Adsorption Characteristics of Activated Carbon Fibers with and without Quaternary Nitrogen Effective for Anion Adsorption Read more
    Editor's pick

    The quaternary nitrogen (N-Q) has been found to be an effective adsorption site for nitrate ions. However, in addition to N-Q, there are many functional groups such as C-π sites on activated carbon fibers (ACFs), and these functional groups have various effects on the adsorption capacity. Understanding the properties of functional groups other than N-Q can be expected to further improve ACFs adsorption performance. In this paper, the authors prepared the ACFs with and without N-Q and examined their adsorption properties.

  • Volume 68 (2020) Issue 9 Pages 823-831
    Nonheme Iron- and 2-Oxoglutarate-Dependent Dioxygenases in Fungal Meroterpenoid Biosynthesis Read more
    Editor's pick

    The fungal meroterpenoid biosynthetic pathways exhibit an abundance of unusual chemistries and interesting enzyme reactions, including those of the multi-functional non-heme Fe(II)- and 2-oxoglutarate-dependent oxygenases that perform selective C–H activation/functionalization with unusual substrate promiscuity and catalytic versatility. Structure–function studies of these remarkable enzymes provide an excellent platform for the development of useful biocatalysts for synthetic biology to create novel molecules for drug discovery.

  • Volume 68 (2020) Issue 9 Pages 832-836
    Effect of Rubbing on the Distribution of Topically Applied Drugs into the Hair Follicles Read more
    Editor's pick

    Rubbing actions are often conducted to apply topical formulations onto the skin. However, few studies have reported the reasons for the acceleration of drug permeation through skin after topical application with or without rubbing. In addition, no studies observed the effect of rubbing direction on the skin penetration-enhancement effects. In this paper, the authors investigated the effects of rubbing direction on the skin permeation and disposition of a model hydrophilic drug, caffeine. This paper provides useful information on the effect of rubbing action and rubbing direction on the skin permeation of topically applied drugs.

  • Volume 68 (2020) Issue 9 Pages 864-867
    Iriomoteolides-14a and 14b, New Cytotoxic 15-Membered Macrolides from Marine Dinoflagellate Amphidinium Species Read more
    Editor's pick

    Marine dinoflagellates are well known as rich sources of biologically active compounds possessing unique chemical structures. This paper deals isolation and structure elucidation of two new cytotoxic 15-membered macrolides, iriomoteolodes-14a and 14b, from the marine dinoflagellate Amphidinium species collected off Iriomote Island, Okinawa. The structures including the absolute stereochemistry of eight stereocenters were determined on basis of spectroscopic data and chemical conversion method. These compounds are analogous to known macrolides, amphidinolides O and P, and the biosynthetic relationships for four compounds are also described.

  • 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.