Chemical and Pharmaceutical Bulletin
Online ISSN : 1347-5223
Print ISSN : 0009-2363
ISSN-L : 0009-2363
  • 69 巻 (2021) 7 号 p. 601-607
    Functional Peptides That Target Biomembranes: Design and Modes of Action もっと読む

    Biological membranes are an important target for molecular design. Properly designed membrane-interacting peptides can induce physicochemical and physiological responses in cell membrane and modulate cell structure and function.

  • 69 巻 (2021) 7 号 p. 608-611
    Construction of 7-Diethylaminocoumarins Promoted by an Electron-Withdrawing Group もっと読む

    Previously, the authors developed a cyclization reaction-based turn-on probe (TCC probe) for protein labeling. The TCC probe is characterized by its ability to construct coumarin structures easily by conjugate addition to the ynone moiety, but the reactivity of the probe becomes poor when attempting to improve the fluorescence properties. The authors improved the reactivity by increasing the electron-withdrawing property of the leaving ester group and succeeded in constructing the coumarin skeleton with good yields. These results suggest an easy method to introduce a coumarin skeleton with good fluorescence properties.

  • 69 巻 (2021) 7 号 p. 674-680
    Latent Structure Analysis of Wet-Granulation Tableting Process Based on Structural Equation Modeling もっと読む

    Quality by design (QbD) is an essential concept for modern manufacturing processes of pharmaceutical products. Understanding the science behind manufacturing processes is crucial; however, the complexity of the manufacturing processes makes implementing QbD challenging. In this study, structural equation modeling (SEM) was applied to understand the causal relationships between variables such as process parameters, material attributes, and quality attributes. Based on SEM analysis, a model composed of the above-mentioned variables and their latent factors without including observational data was identified. The results indicate that SEM analysis could be useful for implementing QbD for the manufacturing processes of pharmaceutical products.

  • 69 巻 (2021) 7 号 p. 681-692
    Elaboration of Non-naturally Occurring Helical Tripeptides as p53–MDM2/MDMX Interaction Inhibitors もっと読む

    Because of the wide range of protein-protein interaction surfaces, it is important to develop molecules that satisfy the intrinsic shape recognition of the partner protein. The authors have previously shown that a stable non-naturally occurring helix trimer of all trans-amide-bonded bicyclic β-amino acid inhibits the p53-MDM2/MDMX-helix-helix interaction that plays a role in regulating p53 function. The authors showed herein that modification of the C-terminal/N-terminal residues improved the inhibitory activity, and confirmed that these peptides are membrane-permeable p53-MDM2/MDMX interaction antagonists and can rescue p53 function in cells.

  • 69 巻 (2021) 6 号 p. 503-515
    Target Protein-Oriented Isolations for Bioactive Natural Products もっと読む

    Structure and bioactivities of natural products are often beyond human knowledge and imagination. In this article, the author developed original screening methods based on protein binding activity. Protein beads method and protein plate method were described. Protein beads method led to the discovery of neural stem cell differentiation activators which inhibited Hes1 dimer formation as a new mechanism. The author also developed protein plate method for protein-protein interaction inhibitors to find new cancer drug candidates. Because protein binding ability is tightly related to bioactivity, protein-based natural products isolation is a powerful means to find new candidate medicines.

  • 69 巻 (2021) 6 号 p. 516-525
    Development of Catalytic Reactions for Precise Control of Chemoselectivity もっと読む

    A cooperative catalyst comprising a soft Lewis acid/hard Brønsted base enabled chemoselective activation of a hydroxyl group over an amino group. The present chemoselective catalysis could be applicable for a variety of amino alcohols, including pharmaceuticals, without requiring a tedious protection-deprotection process. Chemoselective enolization and subsequent α-functionalization of carboxylic acid derivatives were also achieved by a redox active catalyst through the radical process, providing unnatural α-amino/hydroxy acid derivatives bearing a complex carbon framework and a diverse set of functionalities. The present chemoselective catalysis described herein offers new opportunities to expand the chemical space for innovative drug discovery research.

  • 69 巻 (2021) 6 号 p. 526-528
    Fluorescent-Oxaboroles: Synthesis and Optical Property by Sugar Recognition もっと読む

    The optical property of fluorescent unit-conjugated aliphatic oxaboroles has been investigated in this featured article. The authors described the synthesis of fluorescent-oxaboroles by originally developed methods and the optical behavior of the boroles with various sugars. The oxaboroles provide good fluorescence quantum yields and selective recognition toward D-ribose and D-ribose-containing molecules. The molecular recognition induced significant fluorescence quenching. The authors also revealed the positive correlation between the LUMO energy of the oxaborole and the relative fluorescence intensity. The property of the boroles showed the possibility of the boron-based NAD sensor probe.

  • 69 巻 (2021) 6 号 p. 537-547
    A New Bitterness Evaluation Index Obtained Using the Taste Sensor for 48 Active Pharmaceutical Ingredients of Pediatric Medicines もっと読む

    Quantitative evaluation for bitterness of pediatric medicine is essential for adherence.  The authors proposed criteria, change in concentration-dependent potential (CCDP), dose-response slope of the sensor outputs of active pharmaceutical ingredients measured by an artificial taste sensor, which is new and useful bitterness evaluation index for 48 pediatric medicines from the recent edition of the WHO model list of essential medicines for children (7th ed., 2019). CCDP by individual basic bitterness sensor well correlated to various physicochemical factors related hydrophilicity and hydrophobicity. Therefore, CCDP proved to be useful as a bitterness evaluation index of APIs in pediatric medicines.

  • 69 巻 (2021) 6 号 p. 564-572
    Discoveries and Syntheses of Highly Potent Antimalarial Troponoids もっと読む

    Novel 25 derivatives of puberulic acid were synthesized by utilizing the authors’ total synthetic route. According to previous structure-activity relationships information, they focused on the carboxylic acid moiety in puberulic acid and converted it into the corresponding esters, amides and ketones. Antimalarial evaluations in vitro and in vivo of these derivatives were carried out and revealed detailed SAR information. It was clarified that several ester and ketone derivatives conserve strong antimalarial activity similar to that of puberulic acid without any obvious toxicity in oral dose of 15 mg/kg.

  • 69 巻 (2021) 5 号 p. 421-431
    A Review on the Phytochemical and Pharmacological Properties of Rosa laevigata: A Medicinal and Edible Plant もっと読む

    This present review aims to achieve a comprehensive and up-to-date investigation in the phytochemistry and pharmacology of Rosa laevigata Michx.. To date, phytochemical investigation has exposed the presence of triterpenoids, flavonoids, tannins, ligands and polysaccharides in this plant. The crude extracts and the purified compounds have demonstrated various pharmacological effects in vitro and in vivo. In conclusion, the chemical profiles together with the modern pharmacological properties have been adequately summarized. These evidences have revealed this plant to be a valuable source for therapeutic foodstuff and more attention should be paid to a better utilization of this plant.

  • 69 巻 (2021) 5 号 p. 444-446
    Novel Cyclohexyl Meroterpenes Produced by Combinatorial Biosynthesis もっと読む

    Structurally diverse fungal meroterpenoids are promising drug seed compounds. To obtain unnatural, novel meroterpene scaffolds, the authors tested combinatorial biosynthesis by co-expressing functionally distinct terpene cyclase (TPC) genes, pyr4, ascF, andB, or cdmG, with the biosynthetic genes for the production of a TPC substrate, (10’R)-epoxyfarnesyl-dimethylorsellinic acid-3,5-methyl ester, in Aspergillus oryzae NSAR1 as a heterologous host. As a result, all of the tested TPCs afforded the same two novel mono-cyclization products. This study provides important information on the substrate scope of the TPCs, and will contribute to the production of unnatural, novel molecules for future drug discovery.

  • 69 巻 (2021) 5 号 p. 456-463
    Preparation of Solifenacin Succinate Functional Particles Embedded in a Gelling–Swelling Layer (PEGS) and Their Formulation in Orally Disintegrating Tablets もっと読む

    The authors developed solifenacin succinate functional drug particles embedded in a gelling–swelling layer (PEGS) made of a three-layer structure consisting of a core drug layer, a gelling–swelling layer, by which both adequate taste-masking of drug and rapid drug elution were successfully achieved. They also optimized incorporation of above PEGS into orally disintegrating tablets (ODTs), by usage of a fibre-shaped microcrystalline cellulose with poor fluidity, which improved the content uniformity of the ODTs, as the crystal fibres became entangled with the PEGS and other additives. Overall, this taste masking system is so unique and propose new platform for taste masking formulation.

  • 69 巻 (2021) 5 号 p. 464-471
    Indole Glycosides from Calanthe discolor with Proliferative Activity on Human Hair Follicle Dermal Papilla Cells もっと読む

    A methanol extract from the underground part of Calanthe discolor Lindl. (Orchidaceae) demonstrated significant proliferative activity against human hair follicle dermal papilla cells (HFDPC). Through bioassay-guided separation of the extract, a new indole glycoside named 6′-O-b-D-apiofuranosylindican was isolated along with six known compounds including three indole glycosides. Among the isolates, three indole glycoside such as 6′-O-b-D-apiofuranosylindican, glucoindican, and calanthoside showed significant proliferative activity. Furthermore, these active indole glycosides upregulated the expression of VEGF and FGF-7 mRNA and protein in HFDPC, which could be the mechanism of their proliferative activity.

  • 69 巻 (2021) 5 号 p. 488-497
    Expansion of Substrate Scope for Nitroxyl Radical/Copper-Catalyzed Aerobic Oxidation of Primary Alcohols: A Guideline for Catalyst Selection もっと読む

    This manuscript reports aerobic oxidation of primary alcohols into aldehydes with nitroxyl radical/copper catalysis. The reaction method reported herein features that the optimum nitroxyl radical/copper salt catalyst combinations differ depending on the substrate. To express this feature, the catalytic reaction field is represented as a circus tent with three shapes of windows, namely, circle, triangle, and square. Copper plates with different nitroxyl radicals are placed under each of the windows, which indicates different nitroxyl radical/copper salt catalyst combinations. Different alcohol substrates are represented in different forms, namely, sphere, tetrahedron, cube. The sphere, tetrahedral, and cubic alcohols pass through the circular, triangular, and square windows, respectively, to be oxidized into aldehydes.

  • 69 巻 (2021) 4 号 p. 303-313
    Synthesis of Non-canonical Amino Acids and Peptide Containing Them for Establishment of the Template for Drug Discovery もっと読む

    Non-canonical amino acid derivatives and the peptides containing such structures are regarded as the attractive scaffold of novel drug candidates. In this featured article, the author describes the development of novel methodologies for the synthesis of them, involving (1) catalytic asymmetric 1,2-addition of N-2-nitrophenylsulfenyl imines, (2) direct chemical transformation such as ring-closing metathesis or asymmetric Friedel–Crafts reaction using hydrophobic anchor-tagged peptidic substrates. The development of (3) novel recyclable organocatalyst by combining the catalytic motif and hydrophobic anchor is also described.

  • 69 巻 (2021) 4 号 p. 360-373
    Design, Synthesis, and Structure–Activity Relationships Study of N-Pyrimidyl/Pyridyl-2-thiazolamine Analogues as Novel Positive Allosteric Modulators of M3 Muscarinic Acetylcholine Receptor もっと読む

    The authors report novel positive allosteric modulators (PAMs) of M3 muscarinic acetylcholine receptor (mAChR) with N-pyrimidyl/pyridyl-2-thiazolamine scaffold. The structure­activity relationships study was rationalized using conformational analyses based on intramolecular interactions, demonstrating that a unique sulfur-nitrogen nonbonding interaction in the N-pyrimidyl/pyridyl-2-thiazolamine moiety is essential for activity. Newly identified compound 3g showed potent in vitro PAM activity for the M3 mAChR with excellent subtype selectivity. Compound 3g also showed a distinct pharmacological effect on isolated smooth muscle tissue from rat bladder and favorable pharmacokinetics profiles, suggesting its potential as a chemical tool for probing the M3 mAChR in further research.

  • 69 巻 (2021) 4 号 p. 391-399
    Reaction of 3-Oxa-2-oxobicyclo[4.2.0]oct-4-ene-1-carboxylate with Dimethylsulfoxonium Methylide もっと読む

    Cycloalkanes with small ring sizes (such as cyclopropanes and cyclobutanes) constitute a basic structural framework of a wide range of natural products. Cycloalkanes play an important role in organic synthesis as they can take part in various types of reactions. The high reactivities can be attributed to the angle and torsional strains. The authors have been interested in the reactivities of small-ring compounds. The reaction between 3-oxa-2-oxobicyclo[4.2.0]​oct-​4-​ene-1​-​carboxylate and dimethylsulfoxonium methylide afforded 3a,4,5,7a-Tetrahydro-7-hydroxy-benzofuran-6-carboxylate and/or 2-hydroxybicyclo[4.1.0]hept-2-ene-3-carboxylate. A plausible reaction mechanism has been shown.

  • 69 巻 (2021) 4 号 p. 400-406
    Evaluation of Disappearance Time and Palatability of Foams in the Oral Cavities of Healthy Volunteers, and Preparation of Drug-Containing Foam Formulations for Use in the Treatment of Oral Mucositis もっと読む

    Oral mucositis is one of the most common adverse effects of radiation and chemotherapy in treatments of cancers. A mouthwash containing drugs is often used for the prevention and treatment of oral mucositis. In this study, the authors indicated the disappearance time and palatability in the oral cavities of healthy volunteers in placebo foam formulations. In addition, foam formulations of drugs for use as a prevention and treatment of oral mucositis were prepared. This is the first report in regard to foam formulations containing drugs for oral mucositis, and these formulations could be potentially useful in treatments of cancers.

  • 69 巻 (2021) 3 号 p. 237-245
    Impact of COVID-19 Outbreak on the Long-Range Transport of Common Air Pollutants in KUWAMS もっと読む

    To evaluate the impact of air pollutants long-range transported from the Asian continent on the atmospheric environment in Japan, a background site in the top of Noto peninsula, the Kanazawa University Wajima Air Monitoring Station (KUWAMS), has been used for continuous observation since 2004. Among the numerous reports on air pollution during the COVID-19 pandemic, this article proves for the first time that the implementation of the lockdown policy in China reduced both the air pollution in domestic China and that involved in the long-range transport to KUWAMS, including fine (PM2.5) and ultrafine particulates (PM1.0), Organic Carbon (OC) and Element Carbon (EC).

  • 69 巻 (2021) 3 号 p. 281-285
    Boronic Acid-Catalyzed Final-Stage Site-Selective Acylation for the Total Syntheses of O-3′-Acyl Bisabolol β-D-Fucopyranoside Natural Products and Their Analogues もっと読む

    The site-selective transformation provides a powerful strategy for synthesizing complex and diverse multi-functionalized molecules. In this article, the first total syntheses of O-3’-acyl α-bisabolol β-D-fucopyranoside natural products and their analogues by using boronic acid-catalyzed site-selective acylation in the final stage is described. This approach allows us to construct compound libraries for the purpose of structure–activity relationship studies. The cover art illuminates key feature of this work by characteristic chemical transformation.