Chemical & pharmaceutical bulletin最新文献

{"title":"Unexpected Surprise in the Reactions of Acetals and Trialkylsilyl Chloride (R₃SiCl): Efficient Deprotection of Aromatic Acyclic Acetals.","authors":"Muthu Karuppasamy, Ishani Uditha Wedage, Mohamed S H Salem, Koji Morimoto, Shinobu Takizawa, Hiromichi Fujioka","doi":"10.1248/cpb.c24-00837","DOIUrl":"https://doi.org/10.1248/cpb.c24-00837","url":null,"abstract":"<p><p>The reaction of acetals with trialkylsilyl chloride (R₃SiCl) leads to the deprotection of the acetal group, resulting in the corresponding carbonyl compounds. Notably, aromatic dialkyl acetals yield the corresponding parent aromatic aldehydes and ketones in good yields. The reaction conditions are very mild, allowing many acid-labile functional groups to survive without any problems. Additionally, we clarified the reaction mechanism through an NMR study.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"396-400"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143977949","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":"Self-assembly of Urea Derivatives into Supramolecular Gels.","authors":"Masamichi Yamanaka, Shinya Kimura","doi":"10.1248/cpb.c25-00084","DOIUrl":"https://doi.org/10.1248/cpb.c25-00084","url":null,"abstract":"<p><p>In this review, we present our development of low-molecular-weight gelators (LMWGs) with urea moieties. A C₃-symmetric tris-urea framework was found to be an excellent structure for LMWG. Tuning the molecular structure has enabled the creation of LMWGs that gel in a wide range of media, ranging from organic solvents to water. The introduction of appropriate functional groups into LMWGs can be reflected in a function of the resulting supramolecular gel. Our developed supramolecular gels were applied as substrates for electrophoresis, and the separation of proteins and DNA was achieved. Considering material applications, we also developed structurally simplified mono-urea derivatives as LMWGs.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 6","pages":"497-510"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198341","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":"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":"<p><p>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 K_D 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.</p>","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}

{"title":"Efficient Drug Release from Liposomes Introduced Tetrazine Derivatives with Pyrimidine Rings Using Click Chemistry.","authors":"Mizuho Yamasaki, Masayuki Munekane, Kento Kannaka, Kohei Sano, Toshihide Yamasaki, Takahiro Mukai","doi":"10.1248/cpb.c24-00591","DOIUrl":"10.1248/cpb.c24-00591","url":null,"abstract":"<p><p>We developed a novel drug release method using a bioorthogonal inverse electron demand Diels-Alder reaction on liposomal membranes. Based on reports that replacing pyridine with pyrimidine in tetrazine derivatives improves the reaction rate with strained dienophiles, we investigated if liposomes with tetrazine derivatives containing pyrimidine rings efficiently release drugs via click chemistry. We synthesized and evaluated a tetrazine compound (Tz2) bearing a pyrimidine ring. The reaction rate constant of Tz2 with a norbornene (NB) derivative, 5-norbornenecarboxylic acid (NBCOOH), was higher than that of Tz1 with a pyridine ring. Liposomes containing the synthesized Tz2 (Tz2-liposomes) were prepared, and the reaction between Tz2 and NBCOOH on the liposomal membranes was confirmed using high-resolution mass spectrometry. We encapsulated indium-111-labeled diethylenetriaminepentaacetic acid ([¹¹¹In]In-DTPA) in liposomes as a model drug. The release of [¹¹¹In]In-DTPA from Tz2-liposomes was observed after the addition of NBCOOH, with release dependent on NBCOOH concentration. Moreover, release from Tz2-liposomes was significantly higher than that from Tz1-liposomes. These results suggested that tetrazine derivatives with pyrimidine rings efficiently released drugs, likely due to enhanced reaction rates. These findings would advance the development of controlled drug release methods using click chemistry.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 2","pages":"108-111"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490975","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":"Effect of Alcohols on the Skin Permeation of Various Drugs.","authors":"Yuki Ofuchi, Haruna Setoyama, Tsubasa Miyoshi, Kumi Kawano, Yoshiyuki Hattori, Yasuko Obata","doi":"10.1248/cpb.c24-00716","DOIUrl":"10.1248/cpb.c24-00716","url":null,"abstract":"<p><p>In this study we have focused on three types of alcohols: ethanol (EtOH), 2-propanol (IPA), and 1-propanol (NPA), and examined the skin permeability of drugs with different physicochemical properties: ketoprofen (KPF; hydrophobic), cimetidine (CMT; slightly hydrophobic), and caffeine (CF; hydrophilic). The results revealed EtOH particularly enhanced the skin permeation of CF, while IPA enhanced skin permeation regardless of the type of drug. In contrast, NPA significantly increased the skin permeability of KPF and CMT, but had little effect on CF. The differing effects of the alcohols on skin permeation appear to be linked to the physicochemical properties of the drugs. KPF is more hydrophobic than the other drugs, suggesting that it uses the intercellular pathway in the stratum corneum for permeation. CMT has intermediate properties between hydrophilic and hydrophobic, resulting in low skin permeability and ineffective utilization of both the transepidermal and transappendageal pathways. CF mainly utilized the transappendageal pathways for skin permeation because of its smaller molecular weight and more hydrophilic as compared with the other drugs. These results suggest that the effect of different alcohols on enhancing drug skin permeation is not uniform and that the optimal alcohol for enhancing permeability may vary depending on the drug. Therefore, the selection of appropriate additives based on the physicochemical properties of the drug, such as hydrophilicity, hydrophobicity, and molecular weight, is crucial for developing effective transdermal formulation.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"291-297"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771442","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":"Evaluation of Time-Dependent Deformation Behavior of Pharmaceutical Excipients in the Tableting Process.","authors":"Daisuke Mizunaga, Satoru Watano","doi":"10.1248/cpb.c24-00710","DOIUrl":"https://doi.org/10.1248/cpb.c24-00710","url":null,"abstract":"<p><p>Tableting is a critical process in the manufacture of pharmaceutical tablets that directly influences product quality. Ensuring consistent quality between the research and development phase and commercial-scale production is essential during scale-up. In this study, we investigated methods for evaluating time-dependent deformation behavior using four excipients that exhibit different compression deformation behaviors. Dicalcium phosphate dihydrate (DCPD) shows no viscoelasticity, whereas lactose monohydrate (LAC), cornstarch (CS), and microcrystalline cellulose (MCC) exhibit viscoelasticity and viscoplasticity, although the degree of viscosity varies between them. In addition to investigating the known strain rate sensitivity (SRS), we performed mechanical energy evaluation based on the area under the force-displacement curve and stress relaxation tests. A trapezoid waveform was applied during the test, with loading punch speeds of 0.5 and 100 mm/s, and a dwell time of 4.5 s. The SRS value for DCPD approached approximately one, indicating no speed dependence, and the SRS increased in the order of LAC < MCC < CS, consistent with previous studies that used a saw-tooth waveform. Among the mechanical energies, the ratio of plastic flow energy to plastic energy, which depends on dwell time, followed a similar trend to SRS for the three materials other than DCPD. We conclude that axial stress relaxation is affected by machine deformation, whereas radial stress relaxation provides insight into the viscous behavior of the material. Under the test conditions, the effects of the punch-displacement profile and compression pressure on the mechanical energy and stress relaxation were more pronounced than those of SRS.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"213-226"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699676","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":"A New Class of Hybrid Anti-inflammatory Agents of Silibinin A Modified Using Gamma Irradiation.","authors":"Gyeong Han Jeong, Hanui Lee, Byung Yeoup Chung, Hyoung-Woo Bai","doi":"10.1248/cpb.c25-00040","DOIUrl":"https://doi.org/10.1248/cpb.c25-00040","url":null,"abstract":"<p><p>Silibinin is the major active constituent of the medicinal plant milk thistle seeds and possesses hepatoprotective functions. In this study, silibinin A was irradiated with gamma rays to produce 2 novel flavonolignans, silibinosins A (2) and B (3). The structures of these compounds were determined using spectroscopy and spectrometry. The anti-inflammatory effects of the flavonolignan derivatives were assessed using lipopolysaccharide (LPS)-stimulated RAW264.7 and DH82 macrophages. Silibinosin A (2) effectively suppressed the LPS-induced overproduction of pro-inflammatory mediators and cytokines in murine RAW264.7 cells. Western blot analysis revealed that compound 2 decreased the LPS-induced expression of inducible nitric oxide synthase, cyclooxygenase, and phosphorylated nuclear factor-κB and inhibitor-κBα compared to the original silibinin. Furthermore, the inhibitory effects on nitric oxide and prostaglandin E₂ production were observed in LPS-stimulated DH82 canine macrophages. Our results suggest that the newly generated flavonolignans can be novel anti-inflammatory agents for use as therapeutics or ingredients in functional foods.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 4","pages":"401-411"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143978405","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":"Systematic Review of Natural Briaranes in Marine Organisms (2020-2024): Chemical Structures and Bioactivities.","authors":"Li-Guo Zheng, Yu-Chia Chang, Yu-Chi Tsai, Yi-Hao Lo, Wei-Chiung Chi, Mingzi M Zhang, Lun Kelvin Tsou, Zhi-Hong Wen, Tsong-Long Hwang, You-Ying Chen, Ping-Jyun Sung","doi":"10.1248/cpb.c25-00255","DOIUrl":"https://doi.org/10.1248/cpb.c25-00255","url":null,"abstract":"<p><p>This review summarizes the structures, names, and bioactivities of 207 briarane-type diterpenoids, including 113 newly identified metabolites, isolated between 2020 and 2024. All the briaranes discussed were derived from octocorals belonging to the genera Briareum, Dichotella, Ellisella, Junceella, and Erythropodium. Some of these compounds have demonstrated potential biomedical activities.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 7","pages":"581-594"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552464","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":"¹H-NMR-Based Biochemometric Strategy to Identify Transient Receptor Potential Vanilloid 1-Stimulating Compounds from Alpinia officinarum Rhizome.","authors":"Tomohisa Kanai, Tatsuya Shirahata, Shunsuke Nakamori, Rin Sato, Akito Hayashi, Yota Koizumi, Kenichiro Nagai, Susumu Ohkawara, Takayuki Hoshino, Toshiko Tanaka-Kagawa, Hideto Jinno, Yoshinori Kobayashi","doi":"10.1248/cpb.c24-00707","DOIUrl":"https://doi.org/10.1248/cpb.c24-00707","url":null,"abstract":"<p><p>This study established a ¹H-NMR-based biochemometric approach for the isolation of biologically active compounds from complex extracts. In both pharmacognosy and natural product chemistry, reliably isolating bioactive compounds typically necessitates repeating time-consuming and laborious isolation and purification steps, presenting a bottleneck in many studies. We applied biochemometric methods to accurately estimate active compounds, thus minimizing the number of assays and isolation steps. The rhizomes of Alpinia officinarum Hance (Zingiberaceae) have been continuously prescribed in traditional Japanese medicine as stomachics and analgesics, despite a limited understanding of the mechanisms underlying these effects. Additionally, transient receptor potential vanilloid subtype 1 (TRPV1) plays a role in modulating nociception, respiratory defense responses, and gastrointestinal protection. Accordingly, ¹H-NMR-based biochemometry was employed to search for TRPV1-active components in A. officinarum rhizome extracts by combining TRPV1 activity intensity with ¹H-NMR data. However, initially, the active component could not be identified because the principal component analysis loading plot primarily displayed only buckets of primary metabolites. Consequently, we applied orthogonal partial least squares to the ¹H-NMR spectra, which allowed us to identify specific spectral bins at 1.66 ppm (aliphatic) and 7.02, 6.98, 6.82, and 6.74-6.58 ppm (aromatic), correlating with TRPV1-stimulating activity. Based on this prediction, diarylheptanoids were swiftly identified, and their potential to activate TRPV1 was confirmed by administering the identified compounds to TRPV1-expressing cells. These findings highlight the potential of chemometric analysis using ¹H-NMR spectroscopy for identifying the chemical classes responsible for the bioactive properties of complex crude drug extracts.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"195-204"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584865","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":"Identification of a Novel Retinoid X Receptor Agonist from Boenninghausenia albiflora var. japonica.","authors":"Ryura Tateiwa, Yudai Nakama, Ayaka Murase, Tomoki Mizoguchi, Makoto Inoue, Ken-Ichi Nakashima","doi":"10.1248/cpb.c24-00728","DOIUrl":"https://doi.org/10.1248/cpb.c24-00728","url":null,"abstract":"<p><p>Retinoid X receptors (RXRs) are nuclear receptors involved in various crucial biological processes, such as gene regulation, metabolism, and cell differentiation. They predominantly function as heterodimers with other nuclear receptors and modulate gene expression in response to ligand binding. Additionally, they act as therapeutic targets for different conditions, such as cancer and metabolic disorders. Although synthetic RXR agonists, such as bexarotene, are used in clinical settings, they exert adverse side effects. In this study, to explore insights into potential natural RXR agonists as alternatives to existing drugs, we isolated 14 coumarins, including 1 new compound from Boenninghausenia albiflora var. japonica (Rutaceae). Among them, daphnoretin methyl ether (14), a known biscoumarin, was found to exhibit subtype-nonspecific RXR agonist activity.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"73 3","pages":"173-178"},"PeriodicalIF":1.5,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584870","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}