Chemical & pharmaceutical bulletin最新文献_第10页

Unusual Enzymatic C–C Bond Formation and Cleavage Reactions during Natural Product Biosynthesis 天然产物生物合成过程中不寻常的酶促 C-C 键形成和裂解反应

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-03-01 DOI: 10.1248/cpb.c23-00889

Richiro Ushimaru

引用次数: 0

Construction of Biosensing System for Glycated Albumin Using an Electron Transfer Peptide-Modified Protein Probe 利用电子转移肽修饰蛋白探针构建糖化白蛋白生物传感系统

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-03-01 DOI: 10.1248/cpb.c23-00702

Michiru Ito, Kazuharu Sugawara

{"title":"Construction of Biosensing System for Glycated Albumin Using an Electron Transfer Peptide-Modified Protein Probe","authors":"Michiru Ito, Kazuharu Sugawara","doi":"10.1248/cpb.c23-00702","DOIUrl":"https://doi.org/10.1248/cpb.c23-00702","url":null,"abstract":"Glycated albumin (GA) is one of the proteins that replaces several sugar moieties and can be used as an indicator of diabetes mellitus. We developed a sensing system that uses GA in the early detection of diabetes mellitus. In this study, H6Y4C acetylated (Ac-) at the N-terminals of the peptide was combined with wheat germ agglutinin (WGA) to recognize glucose moieties. The Ac-H6Y4C-WGA was constructed as a GA-sensing probe. The tyrosine residues of Y4C exhibited an oxidation peak, and His-tag moieties were introduced to separate Ac-H6Y4C-WGA in the synthesis of the probe. The Ac-H6Y4C-WGA probe binds with the 1–2 molecules of Ac-H6Y4C per WGA using matrix assisted laser desorption/ionization-time of flight (MALDI-TOF)-MS. Next, the functions of Ac-H6Y4C-WGA were evaluated using voltammetry. The number of electron-transfers was calculated based on the relationship between the peak potential and logarithm of scan rate and was 3.03. In the electrochemical measurements with mannose and bovine serum albumin, the peak currents were similar to that of GA alone. By contrast, a decrease in the peak current was suppressed when glucose was added to the solution containing the probe. As a result, Ac-H6Y4C-WGA was selectively bound to the glucose moieties of GA. The calibration curve via differential pulse voltammetry was proportional to the concentrations of GA and ranged from 1.0 × 10−12 to 2.0 × 10−11 M with a detection limit of 3.3 × 10−13 M.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/3/72_c23-00702/figure/72_c23-00702.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"3 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140018991","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 a Water Soluble Self-assembling Analogue of Vizantin 开发水溶性维赞汀自组装类似物

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-27 DOI: 10.1248/cpb.c23-00716

Mayo Nakano, Kyohei Sakamoto, Naoto Yamasaki, Yui Asano, Masataka Oda, Hironobu Takahashi, Takashige Kawakami, Masahisa Inoue, Hirofumi Yamamoto

{"title":"Development of a Water Soluble Self-assembling Analogue of Vizantin","authors":"Mayo Nakano, Kyohei Sakamoto, Naoto Yamasaki, Yui Asano, Masataka Oda, Hironobu Takahashi, Takashige Kawakami, Masahisa Inoue, Hirofumi Yamamoto","doi":"10.1248/cpb.c23-00716","DOIUrl":"https://doi.org/10.1248/cpb.c23-00716","url":null,"abstract":"Vizantin, 6,6′-bis-O-(3-nonyldodecanoyl)-α,α′-trehalose, has been developed as a safe immunostimulator on the basis of a structure–activity relationship study with trehalose 6,6′-dicorynomycolate. Our recent study indicated that vizantin acts as an effective Toll-like receptor-4 (TLR4) partial agonist to reduce the lethality of an immune shock caused by lipopolysaccharide (LPS). However, because vizantin has low solubility in water, the aqueous solution used in in vivo assay systems settles out in tens of minutes. Here, vizantin was chemically modified in an attempt to facilitate the preparation of an aqueous solution of the drug. This paper describes the concise synthesis of a water-soluble vizantin analogue in which all the hydroxyl groups of the sugar unit were replaced by sulfates. The vizantin derivative displayed micelle-forming ability in water and potent TLR-4 partial agonist activity.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00716/figure/72_c23-00716.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"4 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139979223","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

Enhanced Physical Stability of L-Ascorbic Acid in an Ionic Liquid. 增强离子液体中左旋抗坏血酸的物理稳定性

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-21 Epub Date: 2024-01-26 DOI: 10.1248/cpb.c23-00861

Takeshi Oshizaka, Issei Takeuchi, Katsuya Mukae, Kenji Mori, Kenji Sugibayashi

引用次数: 0

Effect of Ag and Ni-Doped Cerium Oxide Nanoparticles on the Formation of ROS and Evaluation as an Alternative Physical Sunscreen Material 掺银和掺镍氧化铈纳米粒子对 ROS 形成的影响及作为替代物理防晒材料的评估

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-21 DOI: 10.1248/cpb.c23-00512

Agnes Giovanni Marsius, Satria Hidayat, Damar Rastri Adhika, Akhmad Zein Eko Mustofa, Veinardi Suendo, Heni Rachmawati

{"title":"Effect of Ag and Ni-Doped Cerium Oxide Nanoparticles on the Formation of ROS and Evaluation as an Alternative Physical Sunscreen Material","authors":"Agnes Giovanni Marsius, Satria Hidayat, Damar Rastri Adhika, Akhmad Zein Eko Mustofa, Veinardi Suendo, Heni Rachmawati","doi":"10.1248/cpb.c23-00512","DOIUrl":"https://doi.org/10.1248/cpb.c23-00512","url":null,"abstract":"CeO2 nanoparticles (nanoceria) were proposed as an alternative physical sunscreen agent with antioxidant properties and comparable UV absorption performance. Green synthesis of nanoceria with Ag and Ni dopants resulted in doped nanoceria with lower catalytic activity and biologically-safe characteristics. The doped nanoceria was characterized using X-ray diffraction (XRD), transmission electron microscopy (TEM), Rancimat Instrument, and UV-Vis Spectrophotometer for SPF (Sun Protection Factor) determination. XRD and TEM analysis showed that nanoceria had been successfully formed in nanoscale-sized with a change in crystallite size due to the crystal defect phenomenon caused by dopant addition. While the Rancimat test and band gap energy analysis were conducted to evaluate the oxidative stability and reactive oxygen species formation, it was confirmed that dopant addition could decrease catalytic activity of material, resulting in Ni-doped Ce with a longer incubation time (11.81 h) than Ag-doped Ce (10.58 h) and non-doped Ce (10.30 h). In-vitro SPF value was measured using the thin layer technique of sunscreen prototype with Virgin Coconut Oil (VCO)-based emulsion, which yielded 10.862 and 5.728 SPF values for 10% Ag-doped Ce and 10% Ni-doped Ce, respectively. The dopant addition of nanoceria could reduce catalytic activity and give a decent in vitro UV-shielding performance test; thus, Ag and Ni-doped nanoceria could be seen as promising candidates for alternative physical sunscreen agents.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00512/figure/72_c23-00512.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"184 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139910106","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

Antiproliferative Activities of Cynaropicrin and Related Compounds against Cancer Stem Cells 三尖杉酯素及相关化合物对癌症干细胞的抗增殖活性

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-20 DOI: 10.1248/cpb.c23-00811

Kousuke Araki, Minami Hara, Shohei Hamada, Takahiro Matsumoto, Seikou Nakamura

{"title":"Antiproliferative Activities of Cynaropicrin and Related Compounds against Cancer Stem Cells","authors":"Kousuke Araki, Minami Hara, Shohei Hamada, Takahiro Matsumoto, Seikou Nakamura","doi":"10.1248/cpb.c23-00811","DOIUrl":"https://doi.org/10.1248/cpb.c23-00811","url":null,"abstract":"Glioblastoma (GBM) has a high mortality rate despite the availability of various cancer treatment options. Although cancer stem cells (CSCs) have been associated with poor prognosis and metastasis, and play an important role in the resistance to existing anticancer drugs and radiation; no CSC-targeting drugs are currently approved in clinical practice. Therefore, the development of antiproliferative agents against CSCs is urgently required. In this study, we evaluated the antiproliferative activities of 21 sesquiterpenoids against human GBM U-251 MG CSCs and U-251 MG non-CSCs. Particularly, the guaianolide sesquiterpene lactone cynaropicrin (1) showed strong antiproliferative activity against U-251 MG CSCs (IC50 = 20.4 µM) and U-251 MG non-CSCs (IC50 = 10.9 µM). Accordingly, we synthesized six derivatives of 1 and investigated their structure–activity relationships. Most of the guaianolide sesquiterpene lactones with the α-methylene-γ-butyrolactone moiety showed antiproliferative activities against U-251 MG cells. We conclude that the 5,7,5-ring and the α-methylene-γ-butyrolactone moiety are both important for antiproliferative activities against U-251 MG cells. The results of this study suggest that the α,β-unsaturated carbonyl moiety, which has recently become a research hotspot in drug discovery, is the active center of 1. Therefore, we consider 1 as a potential lead for developing novel drugs targeting CSCs.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00811/figure/72_c23-00811.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"79 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139910107","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

Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying 喷雾干燥法制备的普罗布考与阿托伐他汀钙三水合物共晶溶解性能的改进

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-16 DOI: 10.1248/cpb.c23-00673

Shinji Oyama, Noriko Ogawa, Kaori Kawai, Kanako Iwai, Toshiya Yasunaga, Hiromitsu Yamamoto

{"title":"Improved Dissolution Properties of Co-amorphous Probucol with Atorvastatin Calcium Trihydrate Prepared by Spray-Drying","authors":"Shinji Oyama, Noriko Ogawa, Kaori Kawai, Kanako Iwai, Toshiya Yasunaga, Hiromitsu Yamamoto","doi":"10.1248/cpb.c23-00673","DOIUrl":"https://doi.org/10.1248/cpb.c23-00673","url":null,"abstract":"A co-amorphous model drug was prepared by the spray-drying (SD) of probucol (PC) and atorvastatin calcium trihydrate salt (ATO) as low water solubility and co-former components, respectively. The physicochemical properties of the prepared samples were characterized by powder X-ray diffraction (PXRD) analysis, thermal analysis, Fourier transform infrared spectroscopy (FTIR), and dissolution tests. Stability tests were also conducted under a stress environment of 40 °C and 75% relative humidity. The results of PXRD measurements and thermal analysis suggested that PC and ATO form a co-amorphous system by SD. Thermal analysis also indicated an endothermic peak that followed an exotherm in amorphous PC and a physical mixture (PM) of amorphous PC and ATO; however, no endothermic peak was detected in the co-amorphous system. The dissolution profiles for PC in the co-amorphous sample composed of PC and ATO were improved compared to those for raw PC crystals or the PM. Stability tests indicated that the co-amorphous material formed by PC and ATO can be stored for 35 d without crystallization, whereas amorphous PC became crystallized within a day. Therefore, co-amorphization of PC and ATO prepared by SD is considered to be a useful method to improve the solubility of PC in water.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00673/figure/72_c23-00673.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"96 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139762447","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

Total Synthesis of Marine Polyketide Plakortone Q 海洋多酮类化合物 Plakortone Q 的全合成

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-03 DOI: 10.1248/cpb.c23-00876

Shinnosuke Okazaki, Kaho Senda, Ayaka Tokuta, Misa Inagaki, Kazuo Kamaike, Koichiro Ota, Hiroaki Miyaoka

引用次数: 0

Synthesis of Coumarin-Conjugated Oligonucleotides via Knoevenagel Condensation to Prepare an Oligonucleotide Library 通过 Knoevenagel 缩合合成香豆素共轭寡核苷酸以制备寡核苷酸库

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00295

Takashi Osawa, Satoshi Obika

{"title":"Synthesis of Coumarin-Conjugated Oligonucleotides via Knoevenagel Condensation to Prepare an Oligonucleotide Library","authors":"Takashi Osawa, Satoshi Obika","doi":"10.1248/cpb.c23-00295","DOIUrl":"https://doi.org/10.1248/cpb.c23-00295","url":null,"abstract":"DNA-encoded libraries (DELs) are attracting attention as a screening tool in the early stages of drug discovery. In the development of DELs, drug candidate compounds are chemically synthesized on barcode DNA. Therefore, it is important to perform the synthesis under mild conditions so as to not damage the DNA. On the other hand, coumarins are gaining increasing research focus not only because they possess excellent fluorescence properties, but also because many medicines contain a coumarin skeleton. Among the various reactions developed for the synthesis of coumarins thus far, Knoevenagel condensation followed by intramolecular cyclization under mild conditions can yield coumarins. In this study, we developed a new synthetic method for preparing a coumarin-conjugated oligonucleotide library via Knoevenagel condensation. The results showed that coumarins substituted at the 5-, 6-, 7-, or 8-positions could be constructed on DNA to afford a total of 26 coumarin-conjugated DNAs. Moreover, this method was compatible with enzymatic ligation, demonstrating its utility in DEL synthesis. The developed strategy for the construction of coumarin scaffolds based on Knoevenagel condensation may contribute to the use of DELs in drug discovery and medicinal chemistry.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00295/figure/72_c23-00295.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"68 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139658665","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

Rational Design of Amphipathic Antimicrobial Peptides with Alternating L-/D-Amino Acids That Form Helical Structures 合理设计具有交替 L-/D 氨基酸并能形成螺旋结构的两性抗菌肽

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-02-01 DOI: 10.1248/cpb.c23-00465

Motoharu Hirano, Hidetomo Yokoo, Nobumichi Ohoka, Takahito Ito, Takashi Misawa, Makoto Oba, Takao Inoue, Yosuke Demizu

{"title":"Rational Design of Amphipathic Antimicrobial Peptides with Alternating L-/D-Amino Acids That Form Helical Structures","authors":"Motoharu Hirano, Hidetomo Yokoo, Nobumichi Ohoka, Takahito Ito, Takashi Misawa, Makoto Oba, Takao Inoue, Yosuke Demizu","doi":"10.1248/cpb.c23-00465","DOIUrl":"https://doi.org/10.1248/cpb.c23-00465","url":null,"abstract":"Antimicrobial peptides (AMPs) are promising therapeutic agents against bacteria. We have previously reported an amphipathic AMP Stripe composed of cationic L-Lys and hydrophobic L-Leu/L-Ala residues, and Stripe exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria. Gramicidin A (GA), composed of repeating sequences of L- and D-amino acids, has a unique β6.3-helix structure and exhibits broad antimicrobial activity. Inspired by the structural properties and antimicrobial activities of LD-alternating peptides such as GA, in this study, we designed Stripe derivatives with LD-alternating sequences. We found that simply alternating L- and D-amino acids in the Stripe sequence to give StripeLD caused a reduction in antimicrobial activity. In contrast, AltStripeLD, with cationic and hydrophobic amino acids rearranged to yield an amphipathic distribution when the peptide adopts a β6.3-helix, displayed higher antimicrobial activity than AltStripe. These results suggest that alternating L-/D-cationic and L-/D-hydrophobic amino acids in accordance with the helical structure of an AMP may be a useful way to improve antimicrobial activity and develop new AMP drugs.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/2/72_c23-00465/figure/72_c23-00465.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"86 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139659095","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