Chemical & pharmaceutical bulletin最新文献_第2页

Improving Pharmaceutical Properties of Thiabendazole through Cocrystallization with Structurally Similar Polyphenol Ligands. 通过结构相似的多酚配体共结晶改善噻苯达唑的药物性能。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c25-00601

Yue Chen, Shuyu Liu

{"title":"Improving Pharmaceutical Properties of Thiabendazole through Cocrystallization with Structurally Similar Polyphenol Ligands.","authors":"Yue Chen, Shuyu Liu","doi":"10.1248/cpb.c25-00601","DOIUrl":"10.1248/cpb.c25-00601","url":null,"abstract":"In this study, two novel thiabendazole (TBZ) cocrystals were successfully prepared by the solvent evaporation method through the selection of structurally similar, highly water-soluble resorcinol (RES) and phloroglucinol (PHG) as cocrystal formers (CCFs), together with TBZ, which is inherently water-insoluble. The two TBZ cocrystals were comprehensively characterized by single-crystal X-ray diffraction (SCXRD), powder X-ray diffraction (PXRD), thermogravimetric-differential scanning calorimetry (TG-DSC), and Fourier-transform IR spectroscopy (FT-IR). Hirshfeld surface analysis was employed to visually illustrate the types and distributions of intermolecular interactions in the two TBZ cocrystals. The solubility and dissolution of the two TBZ cocrystals were measured, respectively. Both cocrystals exhibited superior aqueous solubility compared with TBZ. Specifically, the thiabendazole-phloroglucinol (TBZ-PHG) cocrystal demonstrates that the increased density of hydroxyl groups in the coformer enhances the hydrogen bonding interactions, leading to the formation of a 2 : 1 (TBZ:PHG) stoichiometric cocrystal. The non-parallel arrangement of TBZ molecules in the cocrystal disrupts the close π-π stacking, thereby enhancing solvent penetration. Consequently, its aqueous solubility is improved to a greater extent.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"74 1","pages":"71-78"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145984437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Foreword. 前言。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c26-ctf7408

Kenichiro Todoroki

引用次数: 0

Photoaffinity Electrophoretic Mobility Shift Assay for Analyzing the Binding Specificity of DNA Aptamers to α-Thrombin. 分析DNA适体与α-凝血酶结合特异性的光亲和电泳迁移率转移试验。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c25-00751

Yutaka Sadakane, Akari Tsubokura, Mitsuki Kasai, Yuka Ito, Chihiro Hirai

{"title":"Photoaffinity Electrophoretic Mobility Shift Assay for Analyzing the Binding Specificity of DNA Aptamers to α-Thrombin.","authors":"Yutaka Sadakane, Akari Tsubokura, Mitsuki Kasai, Yuka Ito, Chihiro Hirai","doi":"10.1248/cpb.c25-00751","DOIUrl":"https://doi.org/10.1248/cpb.c25-00751","url":null,"abstract":"DNA aptamers are attractive alternatives to antibodies and advances in selection technologies have yielded several candidate sequences, creating a strong need for efficient methods to evaluate their binding specificity. We previously established a photoaffinity electrophoretic mobility shift assay (EMSA) for analyzing DNA-protein interactions. In this study, we investigated whether this method can be applied to assess the binding specificities of α-thrombin-binding DNA aptamers. The binding specificities of a 15-mer and a 29-mer aptamer were evaluated via photoaffinity EMSA using reaction mixtures enriched in zymogen prethrombin-2, whose structure closely resembles α-thrombin but lacks fibrinogen-clotting activity. Photoaffinity EMSA enabled quantification of the relative binding strengths of α-thrombin and prethrombin-2 resolved in the same sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) lane, revealing that the specificity for α-thrombin was approximately 2.5-3.5-fold higher than that for prethrombin-2 for both aptamers. In the case of the 15-mer aptamer, introducing the photoreactive group at the 9th nucleotide reduced its binding specificity for α-thrombin. This finding indicates that the position of the modification affects aptamer-protein recognition and offers clues about the structural basis of binding. Photoaffinity EMSA also enabled us to distinguish the binding sites of the 15-mer and 29-mer aptamers on α-thrombin using competition experiments with dabigatran and heparin, while allowing selective detection of α-thrombin in human plasma. Together, these results demonstrate that photoaffinity EMSA is a simple and informative approach that can evaluate the binding specificities of multiple DNA aptamers for a target protein in a single SDS-PAGE-based assay.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"74 8","pages":"615-623"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Granulated Ammonium Alginate as a Functional Sodium-Sequestration Agent: Formulation Optimization Using Box-Behnken Design. 造粒藻酸铵作为功能性钠隔离剂：Box-Behnken设计优化配方。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c26-00322

Gosuke Shimada, Yuto Higa, Kazuki Shimogoryou, Maria Yamaguchi, Toru Taharabaru, Yuya Hayashi, Hidenori Takeshita, Taishi Higashi, Keiichi Motoyama

{"title":"Granulated Ammonium Alginate as a Functional Sodium-Sequestration Agent: Formulation Optimization Using Box-Behnken Design.","authors":"Gosuke Shimada, Yuto Higa, Kazuki Shimogoryou, Maria Yamaguchi, Toru Taharabaru, Yuya Hayashi, Hidenori Takeshita, Taishi Higashi, Keiichi Motoyama","doi":"10.1248/cpb.c26-00322","DOIUrl":"https://doi.org/10.1248/cpb.c26-00322","url":null,"abstract":"Excessive salt intake is a major risk factor for cardiovascular, cerebrovascular, and renal diseases, highlighting the need for strategies to reduce intestinal sodium absorption. Ammonium alginate (AAL) suppresses the postprandial increase in blood sodium levels and promotes fecal sodium excretion via ion-exchange and gel-mediated sodium entrapment in the gastrointestinal tract. However, its unpleasant odor and taste, along with its high viscosity upon contact with saliva, cause oral discomfort and limit its practical use in food and clinical settings. In this study, AAL granules were developed to improve their handling and sensory properties while preserving their sodium-sequestration functionality. Granulation with the AQshelax coating was performed using a fluidized-bed granulator, and the process parameters were optimized using a Box-Behnken experimental design. The optimized granules exhibited improved flowability and markedly reduced viscosity upon contact with saliva, resulting in enhanced sensory evaluation scores. In vitro sodium-binding assays demonstrated that the optimized granules retained a sodium-binding capacity comparable to that of unprocessed AAL powder. Furthermore, in salt-loaded mice, granulated AAL maintained its ability to suppress elevated blood sodium levels in vivo. These findings indicate that design-of-experiments-guided granulation successfully overcame key formulation limitations without compromising sodium-sequestration functionality, thereby enabling the practical dietary and clinical application of AAL as a sodium-excreting agent.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"74 9","pages":"708-714"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148982353","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development of Frontier Artificial Nucleoside Derivatives through Precise Nucleic Acid Recognition for Drug Discovery. 基于精确核酸识别的前沿人工核苷衍生物在药物发现中的应用。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c25-00635

Yosuke Taniguchi

引用次数: 0

Characterization of Mechanochemical Solid-State Polymerization for Development of Sulfobetaine Polymer-Drug Conjugates: Design and Synthesis of Artemisinin-Conjugated Novel Methacrylamide Derivatives. 机械化学固体聚合法制备磺胺甜菜碱聚合物-药物缀合物的表征：青蒿素缀合的新型甲基丙烯酰胺衍生物的设计与合成。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c26-00031

Naoki Doi, Yukinori Yamauchi, Yasushi Sasai, Ryosuke Nagai, Madoka Ikawa, Masayuki Kuzuya, Shin-Ichi Kondo

{"title":"Characterization of Mechanochemical Solid-State Polymerization for Development of Sulfobetaine Polymer-Drug Conjugates: Design and Synthesis of Artemisinin-Conjugated Novel Methacrylamide Derivatives.","authors":"Naoki Doi, Yukinori Yamauchi, Yasushi Sasai, Ryosuke Nagai, Madoka Ikawa, Masayuki Kuzuya, Shin-Ichi Kondo","doi":"10.1248/cpb.c26-00031","DOIUrl":"10.1248/cpb.c26-00031","url":null,"abstract":"Artemisinin derivatives (ARTs) induce ferrous iron-dependent cell death (ferroptosis) by generating free radicals. Polymer-ARTs conjugates would be advantageous for cancer therapy. In this paper, we designed and synthesized the three types of ART-conjugated novel methacrylamide derivatives with or without a spacer between the aromatic group and the methacrylamide moiety for mechanochemical solid-state polymerization. The polymer conversion rate of ART-ethyl-MA and ART-methyl-MA for 90 min polymerization was achieved at 78 and 49%, respectively. However, ART-MA, which does not have a spacer, could not polymerize owing to the lowest unoccupied molecular orbital (LUMO) expanding from the methacrylamide moiety to the aromatic sites. The resulting poly(ART-ethyl-MA) produced the thermodynamically stable end-chain radicals through the main-chain scission via mechanical energy, and the generated mechanoradicals would play a role as an initiator of the surrounding monomers. The biocompatible sulfobetaine polymer-ARTs conjugates were fabricated through the mechanochemical solid-state copolymerization of sulfobetaine methacrylate (SBMA) and ART-ethyl-MA. The number average molecular weight and heterogeneity of the resulting water-soluble PSBMA-ARTs conjugates were 8000 g mol-1 and 1.10, respectively. These results suggest that the design of solid monomers suitable for mechanochemical solid-state polymerization would require a molecular structure susceptible to single solid-state electron transfer (SSET) and the stability of mechanoradicals generated by the main-chain scission of resulting polymer. The mechanochemical solid-state copolymerization of zwitterionic monomer and hydrophobic monomer would be advantageous for the development of biocompatible polymer-drug conjugates.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"74 3","pages":"260-268"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Direct Arylation of Juglone Enables Divergent Access to WS-5995 Analogs. 核桃酮的直接芳基化使WS-5995类似物的不同访问成为可能。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c26-00475

Yusuke Akagi, Yoshimi Shimizu, Erika Iwasaki, Yuichiro Taira, Toshiya Komatsu

引用次数: 0

Structure-Guided Engineering of 2-Oxoglutarate-Dependent Oxygenases: Principles, Case Studies, and Emerging Opportunities. 2-氧戊二酸依赖的加氧酶的结构引导工程：原则，案例研究，和新兴的机会。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c25-00652

Yu Nakashima

{"title":"Structure-Guided Engineering of 2-Oxoglutarate-Dependent Oxygenases: Principles, Case Studies, and Emerging Opportunities.","authors":"Yu Nakashima","doi":"10.1248/cpb.c25-00652","DOIUrl":"https://doi.org/10.1248/cpb.c25-00652","url":null,"abstract":"2-Oxoglutarate-dependent non-heme iron oxygenases (2OGX) catalyze a broad spectrum of oxidative transformations, including hydroxylation, halogenation, desaturation, cyclization, rearrangement, and endoperoxidation, through a conserved HxD/E…H facial triad and Fe(IV)=O chemistry. Their functional diversity arises from structural elements that define the catalytic pocket. Substrate-binding architectures can be categorized into four recurrent motifs-the conserved lip (CLip), conserved lid (CLid), specific lid (SL), and dimer lid (DL)-together with the major β-sheet framework (βI-βVI); mutations in these lid/lip elements and within β-strands collectively govern substrate entry, positioning, and radical partitioning. This review discusses representative case studies organized by reaction class-hydroxylation/halogenation, cyclization/rearrangement, endoperoxidation, and free amino acid oxidation-to illustrate how targeted substitutions in these motifs enable rational reprogramming of reactivity. Examples include hydroxylases converted to halogenases, fungal enzymes redirected to construct alternative meroterpenoid scaffolds, endoperoxidases generating non-natural products, and amino acid hydroxylases engineered for halogenation, desaturation, or aziridination. These studies highlight the structural plasticity of 2OGX scaffolds and establish them as programmable biocatalysts, with advances in structural biology and computational design expected to accelerate their application in synthetic biology, natural product discovery, and drug development. The literature published from 2015 through September 2025 is reviewed.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"74 1","pages":"1-15"},"PeriodicalIF":1.3,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Asymmetric Aerobic Intramolecular Dearomative ortho Coupling of Tethered Phenols by Chromium-Salen Complex/Nitroxyl Radical Catalysis. 铬- salen配合物/硝基自由基催化系固酚分子内不对称脱芳邻位偶联。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c25-00762

Shota Nagasawa, Nao Yokota, Shogo Fujiki, Yusuke Sasano, Yoshiharu Iwabuchi

引用次数: 0

Synthesis of Multisubstituted Heterocyclic and Aromatic Compounds Using Catalyst-Controlled Site-Selective Reactions. 用催化剂控制的选择性反应合成多取代杂环和芳香族化合物。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/cpb.c25-00640

Miyuki Yamaguchi

{"title":"Synthesis of Multisubstituted Heterocyclic and Aromatic Compounds Using Catalyst-Controlled Site-Selective Reactions.","authors":"Miyuki Yamaguchi","doi":"10.1248/cpb.c25-00640","DOIUrl":"10.1248/cpb.c25-00640","url":null,"abstract":"Site-selective reactions are important tools in the synthesis of useful multisubstituted compounds, including pharmaceuticals and functional molecules. Such reactions convert functional groups in a selective manner, thereby enabling the synthesis of various compounds with different substitution patterns from a single starting compound. Although a number of transition metal-catalyzed site-selective reactions have been developed, site-selectivity is usually controlled by the substrate, limiting the scope of the reaction. In contrast, catalyst-controlled site-selective reactions of single substrates have been reported, wherein ligand-controlled reactions are of particular interest. Previously, our group developed hydroxyterphenylphosphine ligands to achieve the palladium-catalyzed ortho-selective cross-coupling reactions of dihalogenated phenols/anilines. In this system, the hydroxy groups of the ligand bind to the substrate via the metal, and the proximity of palladium to the halogen at the ortho-position accelerates the reaction at this less reactive position. These reactions have been employed to synthesize multisubstituted benzofurans and indoles from dichlorophenols/anilines using a one-pot ortho-selective Sonogashira coupling/cyclization/Suzuki-Miyaura coupling protocol. The developed catalyst also has enabled the direct C3-selective arylation of N-nonsubstituted indoles, and both tricyclic pyrroloindolines and pyridoindolines have been obtained from tryptamine derivatives via a C3-dearomative arylation/cyclization strategy. Furthermore, the site-selective arylation of N-nonsubstituted 1H-pyrroles has been achieved by changing the ligand, and the reaction proceeded selectively at the C2 or C3 position, yielding 2,2,5-trisubstituted 2H-pyrroles and other compounds whose preparation is challenging via conventional approaches. Finally, the regioselective synthesis of polycyclic aromatic compounds using appropriate palladium catalysts has been performed using the site-selective approach.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"74 2","pages":"132-144"},"PeriodicalIF":1.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146100055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0