Chemical & pharmaceutical bulletin最新文献

{"title":"Evaluation of the Mixing Characteristics of Magnesium Stearate Using Triboelectric Properties.","authors":"Kenta Fujinuma, Masataka Ito, Etsuo Yonemochi, Katsuhide Terada, Hironori Suzuki, Shuji Noguchi","doi":"10.1248/cpb.c24-00694","DOIUrl":"10.1248/cpb.c24-00694","url":null,"abstract":"<p><p>Magnesium stearate (MgSt), which is often used as a lubricant in the production of solid formulations, has different stearic acid and palmitic acid contents depending on the lot and manufacturer, resulting in differences in mixability and lubricating effect. However, there are few reports on the effect of the different physical properties of MgSt samples on mixing and tablet formation. Additionally, it is known that the triboelectric properties of components affect the mixability. Overmixing of formulations can decrease tablet hardness. In this study, the triboelectric properties and mixability of MgSt samples with different lots and manufacturers were evaluated. Tablet hardness was used as an index of the mixability of the MgSt samples with various excipients. The triboelectric properties of the MgSt samples depended on the production lot. Mixability was higher when the triboelectric properties of the excipient and MgSt were different. By evaluating the charge properties of MgSt, it should be possible to select the optimum lot and manufacturer of MgSt for specific formulations.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"78-85"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254710","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}

{"title":"Stereoselective Synthesis of Aromatic Polyketide Prealnumycin.","authors":"Kei Kitamura, Taiki Yamasaki, Hiroto Kaku","doi":"10.1248/cpb.c24-00781","DOIUrl":"10.1248/cpb.c24-00781","url":null,"abstract":"<p><p>Prealnumycin (1), a benzoisochromanequinone compound, produces biologically active exfoliamycin or alnumycin through hybridization with D-ribose or oxidation. We report herein a concise and stereoselective synthesis of 1. The anionic annulation of phthalide 5 with enone 6, prepared via a transition metal-catalyzed enantioselective route, afforded tricyclic lactone 4. This intermediate then underwent a highly diastereoselective introduction of an n-propyl group through nucleophilic addition followed by silane reduction. Subsequent regioselective arene oxidation of 18 using cerium(IV) ammonium nitrate (CAN) afforded naphthoquinone 2. Further manipulations, including acidic deprotection and elimination, yielded prealnumycin in 8 steps.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"86-93"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254712","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}

{"title":"Elucidating Molecular State of Loxoprofen in Acrylic Adhesive Patches Which Could Relate Transdermal Drug Permeability.","authors":"Nanami Haraguchi, Yutaro Watanabe, Manabu Shimazaki, Mika Yoshimura Fujii, Vasanthi Palanisamy, Toshiro Fukami","doi":"10.1248/cpb.c23-00853","DOIUrl":"10.1248/cpb.c23-00853","url":null,"abstract":"<p><p>The purpose of this study was to investigate the effect of the interaction between hydrophilic drugs and acrylic polymers in the adhesive layer of matrix-type patches on skin permeability. Loxoprofen is a nonsteroidal anti-inflammatory drug which has poor permeability. To improve that, patches were prepared using loxoprofen sodium hydrate (LP-Na) as the active pharmaceutical ingredient and acrylic polymers with four different functional groups with different molecular weights. In addition, to enhance the permeability of the patches, we add the lactic acid (LA) as an additive. The crystalline state of the patches was examined by polarizing microscopy and powder X-ray diffraction. The interaction between LP-Na and acrylic polymers was also evaluated using ¹H-NMR. The drug release rate and in vitro skin permeation from the patches were evaluated by dissolution apparatus (paddle method) and Franz diffusion cell, respectively. In patches using acrylic polymers with carboxy groups (AO), the skin permeation test suggested that the LP-Na_AO patch system showed 2.5 times better permeability compared with other patches. Interestingly, addition of LA (LP-Na_AO + LA) also improved 1.5 times more diffusion rate than LP-Na_AO patch and other systems. The interaction of LP-Na with acrylic polymers and LA as pH modifier would enhance the permeability of LP from matrix-type adhesive patches.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"298-306"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771444","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}

{"title":"Development of Fluorescent Estrogen Receptor Ligands with pH Sensor Functionality.","authors":"Tomoya Hirano, Daisuke Yasuda, Takeshi Yamada, Hiroyuki Kagechika","doi":"10.1248/cpb.c24-00685","DOIUrl":"https://doi.org/10.1248/cpb.c24-00685","url":null,"abstract":"<p><p>Estrogen receptors (ERs) and their ligands regulate a variety of physiological processes in humans, and altered ER signaling is associated with serious disorders, including breast cancer. Estrogens also bind to other receptors such as G-protein-coupled receptor 30 (GPER), and so fluorescent estrogen ligands would be useful for various functional studies and for development of drug candidates. Here we describe fluorescent estrogen receptor ligands based on 3-aryl-7-hydroxycoumarin. Notably, these ligands also function as pH-dependent OFF-ON-OFF type fluorescent sensors, enabling the detection of specific ranges of pH.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"412-418"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953911","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}

{"title":"Determination of the Absolute Configuration of 2'-Amino-3'-methylacetophenone Based on the Modified Mosher and Microcrystal Electron Diffraction Methods.","authors":"Hironobu Arita, Tsukasa Tomizawa, Shuntaro Kikukawa, Haruka Sakata, Mizuha Nishimoto, Hidetsugu Tabata, Kayo Nakamura, Tetsuta Oshitari, Hideaki Natsugari, Takenori Kusumi, Hideyo Takahashi","doi":"10.1248/cpb.c25-00284","DOIUrl":"https://doi.org/10.1248/cpb.c25-00284","url":null,"abstract":"<p><p>This study investigated the application of Corey-Bakshi-Shibata (CBS) catalysts to asymmetric reduction of 2'-aminoacetophenone derivatives and determined their absolute configuration using the modified Mosher and microcrystal electron diffraction methods. The results reveal that stereoselective CBS reduction is effective on 2'-amino-3'-methylacetophenone, yielding secondary alcohol, and that the reaction proceeds stereoselectively, even on the gram scale. Moreover, (R)-(-)-secondary alcohol configuration was obtained using an (S)-Me-CBS catalyst, and the stereoselectivity of the reduction followed a previously proposed reaction mechanism for acetophenone derivatives. Thus, this study demonstrated that secondary alcohol could be obtained with the expected stereoselectivity, although requiring a slightly higher amount of the CBS catalyst. The study findings suggest that the amino group of aniline may affect the progress of CBS reduction but does not significantly affect the transition state.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 6","pages":"520-525"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144274274","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}

{"title":"Dynamic Dialysis Method for Characterizing Ammonia-Driven Drug Release from Liposomal Doxorubicin: Applicability and Kinetic Modeling.","authors":"Yoshinori Maeda, Yuki Takechi-Haraya, Emi Kawarai, Yasuhiro Abe, Norihito Shibata, Yoji Sato, Kumiko Sakai-Kato","doi":"10.1248/cpb.c25-00086","DOIUrl":"https://doi.org/10.1248/cpb.c25-00086","url":null,"abstract":"<p><p>Characterizing the complex drug release profiles of nanoparticle-based pharmaceuticals is essential to ensure their efficacy and safety. In this study, we investigated the drug release of a representative liposomal drug, Doxil, to explore the applicability of the dynamic dialysis method (DDM), which offers the advantage of simple implementation. The DDM demonstrated considerable doxorubicin release from Doxil in response to increased ammonia concentration, supporting the hypothesis of ammonia-driven drug release from Doxil in tumor environments. To analyze the drug release of liposomal doxorubicin, we developed a mathematical model that (i) does not require strict sink conditions and (ii) avoids introducing numerous kinetic parameters. This model consolidates the complexities of drug partitioning into the liposomal membrane into a single apparent permeability constant. The release profiles of Doxil at 25°C and a physiological temperature of 40°C were successfully reproduced by the kinetic model, yielding reasonable permeability coefficients of 1.4 × 10^-10 and 2.1 × 10^-10 cm/s, respectively. Our model described the release behavior of the generic product Lipodox, yielding a permeability coefficient of 2.1 × 10^-10 cm/s at 40°C, thereby confirming the utility of the DDM across products. Our results demonstrate that, with optimized conditions, the DDM can assess the drug release kinetics of liposomal doxorubicin. Furthermore, we believe that our study provides a valuable framework for evaluating and optimizing drug release phenomena in liposomal formulations.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 6","pages":"559-567"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526589","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}

{"title":"2-Azanorbornane-Based Amino Amide Organocatalysts for Asymmetric Michael Addition of β-Keto Esters with Nitroolefins.","authors":"Huang Yueming, Rei Togashi, Zubeda Begum, Chigusa Seki, Yuko Okuyama, Eunsang Kwon, Koji Uwai, Michio Tokiwa, Suguru Tokiwa, Mitsuhiro Takeshita, Hiroto Nakano","doi":"10.1248/cpb.c25-00296","DOIUrl":"https://doi.org/10.1248/cpb.c25-00296","url":null,"abstract":"<p><p>Newly designed optically active cage type 2-azanorbornane-based amino amide organocatalysts were developed and employed in the asymmetric Michael addition of β-keto esters with nitroolefins to afford the chiral Michael adducts with good chemical yields (up to 99%) and stereoselectivities (up to diastereomeric ratio (dr) = 97 : 3, up to 96% enantiomeric excess (ee)).</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 7","pages":"616-620"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599510","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}

{"title":"Streptospherin A, a New Cancer Stem Cell Inhibitor, Produced by Streptomyces sp. KUSC-240.","authors":"Hiroaki Ikeda, Ami Mimura, Saki Makita, Kayo Funayama, Morihiro Shibasaki, Taiki Suo, Saya Yoshida, Takefumi Kuranaga, Kazutoshi Shindo, Kazuo Furihata, Masaya Imoto, Hideaki Kakeya","doi":"10.1248/cpb.c25-00097","DOIUrl":"https://doi.org/10.1248/cpb.c25-00097","url":null,"abstract":"<p><p>Cancer stem cells (CSCs) are a major cause of tumor recurrence; therefore, using CSC inhibitors is a potential strategy for cancer chemotherapy. We used our previously reported screening system that targets CSCs to identify a new scarce compound, streptospherin A (1), isolated from Streptomyces sp. KUSC-240. The planar structure of 1 was determined by high-resolution-MS (HR-MS) and NMR analysis. Nuclear Overhauser effect spectroscopy correlation and J-resolved heteronuclear multiple bond connectivity analysis revealed the partial relative configuration on the tetrahydropyran ring. Streptospherin A (1) inhibited CSC sphere formation and suppressed the growth of CSCs. These results suggest that streptospherin A (1) is a potential anticancer agent that may target CSCs.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 5","pages":"445-448"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974608","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}

{"title":"Synthesis and Structure-Activity Relationships of Novel Benzofuran Derivatives with Osteoblast Differentiation-Promoting Activity.","authors":"Masafumi Ando, Shota Kawai, Ko Morishita, Shunsuke Takashima, Kazuya Otake, Megumi Yamamoto, Yoshimichi Shoji, Eiichi Hinoi, Tatsuya Kitao, Hiroaki Shirahase","doi":"10.1248/cpb.c24-00664","DOIUrl":"10.1248/cpb.c24-00664","url":null,"abstract":"<p><p>Osteoporosis is caused by an imbalance between bone resorption and formation, which decreases bone mass and strength and increases the risk of fracture. Therefore, osteoporosis is treated with oral resorption inhibitors, such as bisphosphonates, and parenteral osteogenic drugs, including parathyroid hormone and antisclerostin antibodies. However, orally active osteogenic drugs have not yet been developed. In the present study, to find novel candidates for oral osteogenic drugs, various benzofuran derivatives were synthesized and their effects on osteoblast differentiation were examined in mouse mesenchymal stem cells (ST2 cells). Among the compounds tested, 3-{4-[2-(2-isopropoxyethoxy)ethoxy]phenyl}benzofuran-5-carboxamide (23d) exhibited potent osteoblast differentiation-promoting activity, estimated as EC₂₀₀ for increasing alkaline phosphatase activity, and good oral absorption in female rats, resulting in high C_max/EC₂₀₀. Dual-energy X-ray absorptiometry scanning revealed that 23d at 10 mg/kg/d for 8 weeks increased femoral bone mineral density in ovariectomized rats with an elevation in plasma bone-type alkaline phosphatase activity, and micro-computed tomography showed that it increased bone volume, mineral contents, and strength in femoral diaphysis cortical, but not trabecular bone during the experiment period. 23d potently inhibited cyclin-dependent kinase 8 (CDK8) activity, suggesting that its osteoblastogenic activity is mediated by the suppression of CDK8, as previously reported for diphenylether derivatives. In conclusion, the structure-activity relationships of novel benzofuran derivatives were clarified and 3,5-disubstituted benzofuran was identified as a useful scaffold for orally active osteogenic compounds. Compound 23d exhibited potent osteoblastogenic activity through CDK8 inhibition and osteogenic effects in ovariectomized rats, indicating its potential as an orally active anti-osteoporotic drug.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 1","pages":"25-38"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977865","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}

{"title":"Guided Isolation of Isopentenyl Flavonoids from Daphne giraldii Based on the Combination of GNPS and SMART.","authors":"Bo-Yuan Zhao, Ben-Song Xin, Shuang Qiu, Guo-Dong Yao, Xiao-Xiao Huang, Shao-Jiang Song","doi":"10.1248/cpb.c24-00462","DOIUrl":"https://doi.org/10.1248/cpb.c24-00462","url":null,"abstract":"<p><p>Six flavonoids (1-6), including 3 previously undescribed compounds (1-3), were isolated from the dried roots and stem skins of Daphne giraldii Nitsche. The strategy of LC-tandem mass spectrometry-based Global Natural Products Social Molecular Networking (GNPS) molecular network technology and NMR-based Small Molecule Accurate Recognition Technology (SMART) technology facilitated the precise separation of isopentenyl flavonoids in D. giraldii. The structures were determined through comprehensive spectroscopic analysis. Furthermore, all compounds were evaluated for their cytotoxic activity against Hep3B cells. Specifically, compounds 1 and 3 exhibited significant cytotoxicity with IC₅₀ values of 5.52 ± 0.57 and 2.53 ± 0.49 μM, respectively, compared to the positive control sorafenib (IC₅₀ = 7.08 ± 0.23 μM).</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"189-194"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584868","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}