Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
Featured articles
Displaying 21-20 of 249 articles
  • 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.

  • Volume 70 (2022) Issue 1 Pages 74-81
    Gray-box Soft Sensor for Water Content Monitoring in Fluidized Bed Granulation Read more
    Editor's pick

    The authors developed accurate and descriptive three types of gray-box models to enhance process understanding and precise quality control in fluidized bed granulation. These gray-box models were constructed by integrating the heat and mass balance model (white-box model) and locally weighted partial least squares regression (LW-PLSR) model (black-box model). Their applicability was demonstrated using real operating data on a commercial scale with two formulations. Furthermore, the authors proposed the assessment method based on Hotelling’s T2 and Q residual for gray-box models using LW-PLSR, which contributes decision support to select gray-box or white-box model.

  • Volume 69 (2021) Issue 12 Pages 1141-1159
    Development of Lipid Nanoparticles for the Delivery of Macromolecules Based on the Molecular Design of pH-Sensitive Cationic Lipids Read more
    Editor's pick

    Lipid nanoparticles (LNPs) are able to deliver various therapeutic macromolecules, including short interference RNAs, mRNAs, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) ribonucleoproteins, into the cytosol of the target cells through endocytosis followed by membrane fusion-mediated endosomal escape to induce gene silencing, gene expression, and gene editing, respectively. Rational molecular design of pH-sensitive cationic lipid was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms.

  • Volume 69 (2021) Issue 12 Pages 1160-1169
    Imbuing an Old Heterocycle with the Power of Modern Catalysis: An Isoxazolidin-5-one Story Read more
    Editor's pick

    Catalysts have provided new modes of activation that enable the transformation of otherwise inert molecules. Owing to the labile nature of the N–O bond under reductive conditions, isoxazolidin-5-ones have been used as useful b-amino acid surrogates. In the last decade, this century-old heterocycle has experienced a renaissance upon the merger with catalysis, allowing for the synthesis of structurally diversified molecules otherwise difficult to obtain. This review article highlights the author’s research in this emerging field, focusing on the catalytic asymmetric a-functionalization of – and the alkyl nitrene formation from – the heterocycle.

  • Volume 69 (2021) Issue 12 Pages 1170-1178
    Development of Novel Methodology Using Diazo Compounds and Metal Catalysts Read more
    Editor's pick

    The author focuses on expanding metal-carbene chemistry via developing novel reactions, mechanistic analysis based on computational predictions, and synthetic demonstrations for pharmaceutically essential molecules. The findings include that silver-carbenes possess unusual chemical properties, leading to unique chemoselectivities and regioselectivities with stereocontrol. By utilizing the exceptional reactivities, the enantioselective reactions involving silver-carbenes were achieved in studies regarding arene dearomatization. A novel type of insertion reactions was also developed using a designed Rh2(NHCOtBu)4 catalyst, assembling a series of nitrogen-bridged heterocycles. The author believes that the obtained mechanistic profiles could serve as bases for designing novel reactions and advanced catalysis for pharmaceuticals.

  • Volume 69 (2021) Issue 12 Pages 1195-1199
    Synthesis and Evaluation of Quinone Derivatives for Activity against Trypanosome cruzi Read more
    Editor's pick

    Chagas disease is a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi and an important health problem in rural areas of Latin American countries. Safe drugs with high clinical efficacy have been urgently needed. Authors synthesized quinone compounds and evaluated their in vitro antitrypanosomal activity against trypomastigotes and amastigotes of Trypanosoma cruzi. In addition, solubility and membrane permeability were measured to confirm whether compounds with promising antiprotozoal activity had physicochemical properties compatible with oral administration. Among the synthesized compounds, 5a showed adequate antiprotozoal activity, solubility, and high membrane permeability.

  • Volume 69 (2021) Issue 11 Pages 1075-1082
    Design of the N-Terminus Substituted Curvature-Sensing Peptides That Exhibit Highly Sensitive Detection Ability of Bacterial Extracellular Vesicles Read more
    Editor's pick

    The authors rationally designed a series of curvature-sensing peptides, which could selectively detect bacterial extracellular vesicles (EVs) in cultured media.  The most sensitive peptide nFAAV5, in which the N-terminal region of the previosly reported curvature-sensing peptide FAAV was modified, was applicable for quantification of changes in the amount of EVs even in the presence of the EV-secretory bacterial cells.  Therefore, the novel peptide is useful to EV studies as a potent EV-sensing peptide.

  • Volume 69 (2021) Issue 11 Pages 1088-1096
    Design and Optimization of Scored Tablets with Concave Surface and Application of Bayesian Estimation for Solving Scaleup Problem Read more
    Editor's pick

    In view of self-medication, it is valuable to develop patient-friendly scored tablets that possess dividing uniformity. Preparation conditions for a concavely curved scored tablet were optimized, employing a design of experiment and a response surface method incorporating a thin-plate spline interpolation, and a bootstrap resampling technique. To make it possible to scaleup the optimal solution estimated on a trial-scale, a Bayesian estimation was applied. Credible ranges of critical responses in large-scale manufacturing were successfully estimated as a posterior probability from the trial-scale experiment as a prior probability.

  • Volume 69 (2021) Issue 11 Pages 1104-1109
    Bivalent β-Carbolines Inhibit Colorectal Cancer Growth through Inducing Autophagy Read more
    Editor's pick

    Autophagy plays diverse functional roles in various stages of tumor, and numerous drugs targeting autophagy in in-vitro and in-vivo models for colorectal cancer (CRC) have been reported.  In search for novel and effective drugs with minimal cytotoxicity to reduce the mortality rate of CRC, the authors designed and synthesized a series of alkyl diamine linked bivalent β-carbolines, and compound 8 was found to be the most potent antitumor agent against human colon carcinoma cell lines with the IC50 value of less than 5 μM. The mechanism of action study revealed that compound 8 reduced growth of colon cancer cells by inducing autophagy.

  • Volume 69 (2021) Issue 11 Pages 1110-1122
    Discovery of DS68702229 as a Potent, Orally Available NAMPT (Nicotinamide Phosphoribosyltransferase) Activator Read more
    Editor's pick

    Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the rate-limiting step of the NAD+ salvage pathway. Since boosting NAD+ has positive effects on metabolic regulation, activation of NAMPT is an attractive therapeutic approach for the treatment of various diseases, including type 2 diabetes and obesity. Optimization of our previous lead compound led to identification of DS68702229, a potent NAMPT activator with good oral exposure. Oral administration of DS68702229 to high-fat diet-induced obese mice elicited NAD+ level increase in various tissues, ultimately leading to continuous and significant body weight reduction. These observations indicate that DS68702229 is a promising anti-obesity drug candidate.

  • Volume 69 (2021) Issue 10 Pages 931-944
    Site-Selective Molecular Transformation: Acylation of Hydroxy Groups and C–H Amination Read more
    Editor's pick

    Control of site selectivity, selectivity among several identical functional groups, in molecular transformation has become a fundamental issue in synthetic organic chemistry owing to the potential utility for selective modification of biologically active multi-functionalized molecules. In the review article, the authors’ research related to site selectivity in two types of transformations, namely, the acylation of hydroxy groups and C-H amination, is summarized. In catalyst-controlled site-selective transformation, the catalysts choose the reaction point where they feel most comfortable.

  • Volume 69 (2021) Issue 10 Pages 945-946
    Foreword Read more
    Editor's pick

    A variety of topics have been reviewed from the view point of analytical chemistry. The topics include: self-reproducing vesicles led by molecular transformation, characterization and physiological roles of oxidized phospholipids, advantages of small fish as a carcinogenesis model, separation techniques in supercritical fluid chromatography, drug-antibody ratio determination of antibody-drug conjugates, and membrane-based rapid test reagents for point of care testing. All these reviews will provide indispensable information based on analytical chemistry that supports and evolves pharmaceutical sciences as well as biology and medicine.

  • Volume 69 (2021) Issue 10 Pages 1005-1009
    Nitroxyl Radical/Copper-Catalyzed Electrooxidation of Alcohols and Amines at Low Potentials Read more
    Editor's pick

    Accurate quantitative and qualitative analysis of biological and clinical samples is important, and rapid and simple analytical methods are demanded. The authors investigate an electrochemical detection of alcohols and amines by cyclic voltammetry at low potential using nortropine N-oxyl (NNO) and a copper salt as catalysts. As a result, although the concentration that could be quantified with good accuracy was limited in both the detection of alcohols and the detection of amines, a correlation was observed between the current and the concentration.

  • Volume 69 (2021) Issue 10 Pages 1010-1016
    Electrophilic Epoxidation of α,β-Unsaturated Oximes with Dioxiranes and Ring Opening of the Epoxides Read more
    Editor's pick

    α,β-Unsaturated carbonyl compounds undergo nucleophilic reaction at electron-deficient carbon-carbon double bonds, as well as cycloaddition with dienes or 1,3-dipoles having a high HOMO energy levels. This character of the enones and enals can be transformed from electron-deficient to electron-rich by conversion to the corresponding oximes because of the electron-donating ability of an electron pair (umpolung). This paper describes that α,β-unsaturated oximes underwent electrophilic epoxidation with in-situ-generated dimethyldioxirane to give the corresponding epoxides in good yields. Nucleophilic ring-opening reactions of the epoxides afforded α-substituted products. Shi asymmetric epoxidation of the oximes proceeded with moderate asymmetric selectivity.

  • Volume 69 (2021) Issue 10 Pages 1034-1038
    Theoretical Study on the Mechanism of Spirocyclization in Spiroviolene Biosynthesis Read more
    Editor's pick

    Authors uses computational chemistry to scrutinize the biosynthetic mechanism of a diterpenoid, spiroviolene, which features a 5/5/5/5 tetracyclic system with a spirocyclic skeleton. Terpenes/terpenoids are biosynthesized via multiple stable carbocation intermediates, such as tertiary, allyl, and cyclopropylcarbinyl cations. However, formation of secondary carbocations have been proposed in the spiroviolene biosynthesis in earlier reports. On the basis of DFT calculations, authors propose a new 16-step carbocation cascade leading to the spiroviolene skeleton. This cascade bypasses the formation of unstable secondary carbocations by breaking the adjacent C–C bond to form a more stable tertiary carbocation and by Wagner-Meerwein 1,2-methyl rearrangement. 

  • Volume 69 (2021) Issue 9 Pages 819-831
    Molecular Transformation Based on an Innovative Catalytic System Read more
    Editor's pick

    Three hybrid catalysts have been designed based on the reaction mechanism of enzymes. These catalysts using non-covalent intermolecular interactions exhibit remarkable catalytic performance for the activation of α,β-unsaturated amides and carboxylic acids as well as the dynamic kinetic resolution of a racemic electrophile in an SN2-type reaction. These innovative catalytic systems allow the asymmetric synthesis of biologically important molecules such as atorvastatin, beraprost, sitagliptin, and avenaol.

  • Volume 69 (2021) Issue 9 Pages 840-853
    Environmental Risk Assessment of Active Human Pharmaceutical Ingredients in Urban Rivers in Japan Read more
    Editor's pick

    In Japan, environmental risk assessments (ERA) for human pharmaceuticals in aquatic environments have barely begun. This paper reports the first study assessing the validity of ERA guidance issued by the Ministry of Health, Labour, and Welfare in 2016 for new medicinal products in the environment, using selected pharmaceuticals already on the market. The accuracy of predicted environmental concentrations was evaluated by measuring environmental concentrations in urban rivers. The results will be useful information applicable to ERA for new medicinal products, and development of future ERA standards in Japan.

  • Volume 69 (2021) Issue 9 Pages 854-861
    2-Thioxothiazolidin-4-one Analogs as Pan-PIM Kinase Inhibitors Read more
    Editor's pick

    PIM kinases are attractive therapeutic targets for the treatment of multiple hematological malignancies. In search for novel PIM kinase inhibitors, the authors designed and synthesized a series of 5-benzylidene-2-thioxothiazolidin-4-one derivatives with various substitutions at the pyrazine rings. Several compounds exhibited subnanomolar to single-digit nanomolar potencies against all three PIM isoforms and showed anti-proliferative activities against human leukemic EOL-1 and MOLM-16 cell lines. The mechanism of action study of compound 17 clearly revealed that a pan-PIM inhibitor reduced phosphorylation of downstream substrates of PIM kinase such as BAD and 4EBP1 in a dose-dependent manner.