Chemical & pharmaceutical bulletin最新文献_第6页

The Rational Selection for Solubilized Formulation Technologies Utilizing Physicochemical Properties. 利用理化性质合理选择增溶制剂工艺。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00434

Kouya Kimoto, Katsuhiko Yamamoto, Toshiro Fukami, Yukihiro Ikeda

{"title":"The Rational Selection for Solubilized Formulation Technologies Utilizing Physicochemical Properties.","authors":"Kouya Kimoto, Katsuhiko Yamamoto, Toshiro Fukami, Yukihiro Ikeda","doi":"10.1248/cpb.c25-00434","DOIUrl":"10.1248/cpb.c25-00434","url":null,"abstract":"Enhancing the solubility of poorly water-soluble oral small-molecule drugs remains a critical challenge in the pharmaceutical industry, particularly during the early stages of drug development when selecting solubilized formulation technologies. This difficulty largely stems from the absence of objective indicators for comparing formulations. This study aimed to establish the selection indicators for solubilized formulation technologies based on applicable formulation preparation among amorphous solid dispersion (ASD), cyclodextrin (CD), lipid-based formulation (LBF), and nanocrystal (NC), utilizing the overall molecular properties, such as molecular weight, melting point (Tm), Log P, and polar surface area (PSA) in the marketed oral drugs employing solubilized formulation technologies. Single-property plots of the selected properties revealed the regions of higher or lower frequency in the selected molecular properties. The multiple property plot with Tm and the combined property of normalized Log P and PSA identified a specific area as the optimal range for selecting ASD, LBF, and NC, while excluding CD. These findings are expected to function as guide indicators that enable the rational selection of formulation technologies and serve as a foundational approach to accelerating development timelines based on molecular properties available during the early stages of drug development.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 9","pages":"857-867"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085110","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

Structural Change of Neurotransmitter Amine with CO₂ in Water: Formation of Covalently Bound Carbamic Acid. 神经递质胺与CO2在水中的结构变化：共价结合氨基甲酸的形成。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00463

Keitaro Shiota, Ryo Murakami, Fuyuhiko Inagaki

引用次数: 0

A Melittin-Derived Peptide with Improved Cytosolic Delivery Efficiency through Caveolae- and Actin-Mediated Endocytosis. 通过小泡和肌动蛋白介导的内吞作用提高胞质递送效率的蜂毒蛋白衍生肽。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00479

Yoshimasa Kawaguchi, Naoki Tamemoto, Yusuke Uehata, Yusuke Miyazaki, Wataru Shinoda, Shiroh Futaki

{"title":"A Melittin-Derived Peptide with Improved Cytosolic Delivery Efficiency through Caveolae- and Actin-Mediated Endocytosis.","authors":"Yoshimasa Kawaguchi, Naoki Tamemoto, Yusuke Uehata, Yusuke Miyazaki, Wataru Shinoda, Shiroh Futaki","doi":"10.1248/cpb.c25-00479","DOIUrl":"https://doi.org/10.1248/cpb.c25-00479","url":null,"abstract":"Efficient cytosolic delivery of functional proteins such as therapeutic antibodies remains a major challenge in drug development. In this study, we sought to optimize the cytosolic delivery peptide Mel-V8G12, a melittin derivative, through structure-guided design and functional screening of its amino acid substitutions. Among seven derivatives, VG-6, featuring A10L, T11E, and S18K substitutions demonstrated superior cytosolic delivery efficiency compared with the parental Mel-V8G12, while maintaining low cytotoxicity. Notably, VG-6 exhibited enhanced membrane-lytic activity toward neutral lipid membranes, yet did not increase cellular toxicity, suggesting a delivery mechanism distinct from conventional pH-responsive endosomolytic peptides. Mechanistic studies revealed that, in contrast to Mel-V8G12 which predominantly utilizes actin-mediated endocytosis, VG-6 additionally engages caveolae-mediated endocytosis, contributing to its enhanced cytosolic delivery. Furthermore, VG-6 enabled successful cytosolic delivery of functional Cre recombinase and immunoglobulin G (IgG), facilitating biological activity and subcellular targeting. These findings suggest that VG-6 is a promising tool for intracellular delivery of protein therapeutics via a unique membrane-interacting and endocytic pathway.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 9","pages":"896-906"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136864","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

Highly Precise Anomaly Detection Using Multivariate Statistical Process Control with Appropriate Scaling of Input Variables in Pharmaceutical Continuous Manufacturing. 医药连续生产中输入变量适当缩放的多元统计过程控制高精度异常检测。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00652

Takuya Oishi, Takuya Nagato, Chikara Tsujikawa, Takuya Minamiguchi, Sanghong Kim

{"title":"Highly Precise Anomaly Detection Using Multivariate Statistical Process Control with Appropriate Scaling of Input Variables in Pharmaceutical Continuous Manufacturing.","authors":"Takuya Oishi, Takuya Nagato, Chikara Tsujikawa, Takuya Minamiguchi, Sanghong Kim","doi":"10.1248/cpb.c24-00652","DOIUrl":"https://doi.org/10.1248/cpb.c24-00652","url":null,"abstract":"Multivariate statistical process control (MSPC) has attracted considerable attention as a monitoring method for pharmaceutical continuous manufacturing. However, there are few examples of its application in pharmaceutical manufacturing, and previous studies have shown high false-positive rates. One of the reasons is the use of inappropriate scaling factors. In pharmaceutical processes, the number of experiments for MSPC modeling tends to be small because the active pharmaceutical ingredients are expensive. Subsequently, the standard deviation, a common scaling factor for some variables, becomes too small, and the model may become sensitive to small variations. In this study, we have proposed methods for determining the appropriate scaling factors. These methods were applied to granulation and drying processes in pharmaceutical continuous manufacturing. The MSPC model can detect changes in the process parameters and raw materials used during continuous wet granulation and fluidized bed drying using the proposed scaling method.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"234-245"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143750108","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

Unexpected Surprise in the Reactions of Acetals and Trialkylsilyl Chloride (R₃SiCl): Efficient Deprotection of Aromatic Acyclic Acetals. 缩醛与三烷基硅酰氯（R3SiCl）反应中的意外惊喜：芳香无环缩醛的有效脱保护。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c24-00837

Muthu Karuppasamy, Ishani Uditha Wedage, Mohamed S H Salem, Koji Morimoto, Shinobu Takizawa, Hiromichi Fujioka

引用次数: 0

Self-assembly of Urea Derivatives into Supramolecular Gels. 尿素衍生物自组装成超分子凝胶。

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00084

Masamichi Yamanaka, Shinya Kimura

引用次数: 0

Molecular Mechanism of Anti-SARS-CoV-2 Activity of Ephedra Herb Macromolecule Condensed-Tannin Contained in Ephedrine Alkaloids-Free Ephedra Herb Extract. 麻黄提取物中大分子缩合单宁抗sars - cov -2活性的分子机制

IF 1.5 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00191

Masashi Hyuga, Nahoko Uchiyama, Morio Yoshimura, Yoshiaki Amakura, Sumiko Hyuga, Masashi Uema, Genichiro Tsuji, Akinori Nishi, Hiroshi Odaguchi, Yosuke Demizu, Yukihiro Goda

{"title":"Molecular Mechanism of Anti-SARS-CoV-2 Activity of Ephedra Herb Macromolecule Condensed-Tannin Contained in Ephedrine Alkaloids-Free Ephedra Herb Extract.","authors":"Masashi Hyuga, Nahoko Uchiyama, Morio Yoshimura, Yoshiaki Amakura, Sumiko Hyuga, Masashi Uema, Genichiro Tsuji, Akinori Nishi, Hiroshi Odaguchi, Yosuke Demizu, Yukihiro Goda","doi":"10.1248/cpb.c25-00191","DOIUrl":"https://doi.org/10.1248/cpb.c25-00191","url":null,"abstract":"Ephedrine alkaloids-free Ephedra Herb extract (EFE) and its component, Ephedra Herb macromolecule condensed-tannin (EMCT), have been shown to exhibit anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) activity in VeroE6/TMPRSS2 cells. Therefore, it is expected that EFE will be developed as a new natural product drug that exhibits anti-SARS-CoV-2 effects. In this study, we analyzed the molecular mechanism of EMCT's anti-SARS-CoV-2 activity, namely, inhibition of the binding of the viral spike (S) protein to angiotensin-converting enzyme 2 (ACE2), to confirm that EMCT is an active component of the anti-SARS-CoV-2 effect. Furthermore, matrix-assisted laser desorption/ionization time-of-flight-MS of EMCT was performed to determine its molecular mass distribution, resulting in a mass spectrum that exhibited a broad single peak at approximately 60000 and a mass range of m/z 30000-120000. In a binding assay of the receptor-binding domain of the S protein to ACE2, EMCT inhibited this interaction with an IC50 of 48 nM. According to surface plasmon resonance analysis, EMCT binds to both the S protein and ACE2 with KD values of 39 and 44 nM, respectively. Furthermore, the interaction between the predicted substructure of EMCT, flavan-3-ol tetramers, and the S protein was evaluated in silico, indicating that the possible binding site is the ACE2-binding region of the S protein. These results suggest that the anti-SARS-CoV-2 activity of EMCT is exerted through inhibition of S protein/ACE2-mediated viral infection. Therefore, EMCT is thought to be the most useful ingredient for quality control of EFE as an investigational extract drug.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 7","pages":"621-626"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625467","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

Synthetic Study of Caulerpin: Construction of the Core Structure through Gold-Catalyzed Cascade Cyclization of Azido-Alkynes. 杂环胶的合成研究：金催化叠氮烷级联环化构建核心结构。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00268

Hiroaki Ohno, Atsuhito Tsuji, Daiki Hasegawa, Shinsuke Inuki, Norihito Arichi

引用次数: 0

In Silico and in Vitro Evaluation of Synthetic Chalcones against Paracoccidioides brasiliensis. 合成查尔酮对巴西副球虫的室内及体外药效评价。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00044

Giuliano da Conceição Pereira, Jessica Raquel B Monteiro, Felipe Antonio Carvalho da Costa, Marcelo Kurgonas de Oliveira, Eduardo Vieiras Farias, Lorena Carnielli-Queiroz, Carlos Pelleschi Taborda, Juliana Barbosa Coitinho, Reginaldo Bezerra Dos Santos, Rodrigo Rezende Kitagawa, Rita de Cássia Ribeiro Gonçalves

{"title":"In Silico and in Vitro Evaluation of Synthetic Chalcones against Paracoccidioides brasiliensis.","authors":"Giuliano da Conceição Pereira, Jessica Raquel B Monteiro, Felipe Antonio Carvalho da Costa, Marcelo Kurgonas de Oliveira, Eduardo Vieiras Farias, Lorena Carnielli-Queiroz, Carlos Pelleschi Taborda, Juliana Barbosa Coitinho, Reginaldo Bezerra Dos Santos, Rodrigo Rezende Kitagawa, Rita de Cássia Ribeiro Gonçalves","doi":"10.1248/cpb.c25-00044","DOIUrl":"https://doi.org/10.1248/cpb.c25-00044","url":null,"abstract":"Paracoccidioidomycosis (PCM) is an infectious disease caused by dimorphic fungi of the Paracoccidioides genus and causes a series of discomforts in affected patients. This work aimed to evaluate the antifungal potential of synthetic chalcones against Paracoccidioides brasiliensis (Pb) and to determine in silico possible therapeutic targets. An in silico evaluation of a database of 21 synthesized chalcones was carried out based on pharmacokinetic parameters, enzymatic inhibition, Tanimoto similarity, and the prediction of the spectrum of activity by PASS (prediction of activity spectra of substances). The most viable chalcones from the previous evaluation were selected for the measurement of minimum inhibitory concentration (MIC) against Pb and for cytotoxicity assays pre- and post-metabolization using HEPG2 cells. After in silico evaluation, the compounds 4, 11, 12, 20, and 21 were selected to carry out the molecular docking and in vitro tests. In the docking studies, multiple hydrophobic and polar intermolecular interactions were observed, such as hydrogen bonds, with emphasis on compound 20 in the active site of thioredoxin, where it made 4 hydrogen bonds with the residues Gln43, Ala36, and Thr38. In vitro testing revealed antifungal activity, with the MICs ranging from 32 to 128 μg/mL. In cytotoxicity assays, the 5 compounds exhibited reduced IC50 values (5.51-14.85 μg/mL pre-metabolization and 10.48-35.4 μg/mL post-metabolization). The compounds 4, 11, 12, 20, and 21 have shown favorable predictions of pharmacokinetic characteristics and distinct actions compared to conventional medications, as well as antifungal activity with less toxicity after metabolization, making them the best candidates for further studies.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 9","pages":"772-782"},"PeriodicalIF":1.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991541","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

Catalytic Synthesis of Azepinoindoles from Ynamides Containing Indolyl Moieties via Ruthenium-Vinylidene Species. 钌-偏乙烯类催化剂催化含吲哚基苯胺合成氮杂吲哚。

IF 1.3 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/cpb.c25-00355

Masanori Tayu, Ryuta Watanabe, Hiroki Shinshima, Yi Hui, Sayaka Ohrui, Nozomi Saito

引用次数: 0