Chemical & pharmaceutical bulletin最新文献

{"title":"Antihypertensive and Angiotensin I-Converting Enzyme-Inhibitory Effects of the Leaves of Sesamum indicum and Bioactive Compounds.","authors":"Takahiro Kitagawa, Hibiki Tashiro, Takuhiro Uto","doi":"10.1248/cpb.c24-00565","DOIUrl":"https://doi.org/10.1248/cpb.c24-00565","url":null,"abstract":"<p><p>Sesame (Sesamum indicum L.) is an important oilseed crop, and its seeds are a source of edible oil and widely used as a nutritious food that is beneficial to health in oriental countries. Phytochemical and biological investigations of the seeds have been well reported; however, those of the leaves have been limited. To explore the potential value of sesame leaves, we focused on their antihypertensive potency. Oral administration of sesame leaf extract significantly reduced blood pressure in spontaneously hypertensive rats. Next, we examined the angiotensin I-converting enzyme (ACE)-inhibitory activity of sesame leaves, stems, and seeds and observed that the inhibitory potencies of leaves and seeds were stronger than those of stems. Acteoside and pedaliin, the major compounds in the leaves, as well as exhibited ACE inhibitory activity. Furthermore, we determined the content of these compounds in the leaves, stems, and seeds using LC/MS. The contents of both compounds in the leaves were higher than those in the stems and seeds. These results suggest that sesame leaf extract can mitigate hypertension, at least in part, via the inhibition of ACE activity by acteoside and pedaliin, suggesting that sesame leaves may have the potential to be used for treating hypertension.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 12","pages":"1105-1109"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142892449","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":"Synthetic Study towards Providencin: Stereocontrolled Synthesis of the Furan-Substituted Cyclobutanol Segment.","authors":"Yousuke Yamaoka, Ryo Nishina, Ken-Ichi Fujita, Kiyosei Takasu","doi":"10.1248/cpb.c24-00629","DOIUrl":"https://doi.org/10.1248/cpb.c24-00629","url":null,"abstract":"<p><p>This study explores the synthesis of unique furanocembranoid-type marine diterpenoid, providencin. Providencin features a highly oxidized structure with two furan rings, two oxirane rings, and a bicyclo[12.2.0]hexadecane framework. Its potential as a lead compound for drug development has drawn attention to its total synthesis, particularly focusing on the challenging right-half segment involving a highly substituted cyclobutane ring. We developed a novel synthetic strategy for the fragment using a [2 + 2] cycloaddition reaction of lithium ynolates with α,β-unsaturated lactone, successfully constructing a bicyclic cyclobutene structure. Stereoselective hydrogenation of cyclobutenes was achieved by using Crabtree's catalyst under high pressure H₂ atmosphere. After further transformation, the synthesis of the furan-substituted cyclobutanol fragment having a formyl side chain was accomplished.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 11","pages":"966-969"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646928","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 of Biosynthetic Intermediates of Vibrioferrin and Enzyme Reactions Using Them as Substrates.","authors":"Hidemichi Mitome, Tomotaka Tanabe, Tatsuya Funahashi, Kazuki Akira","doi":"10.1248/cpb.c24-00168","DOIUrl":"https://doi.org/10.1248/cpb.c24-00168","url":null,"abstract":"<p><p>Biosynthetic intermediates of siderophore vibrioferrin (VF), O-citryl-L-serine, 2-aminoethyl citrate, and alanine-2-amidoethyl citrate were respectively synthesized as a mixture of stereoisomers. These compounds were used as substrates for enzyme reactions using recombinant PvsA, PvsB, and PvsE proteins as corresponding enzyme equivalents. The results of our study show that each enzyme reacts with a respective substrate and produces VF along the proposed biosynthetic pathway. Furthermore, the results of this study will contribute to the understanding of VF biosynthetic enzymes and may help in the development of antimicrobial drugs by inhibiting siderophore biosynthetic enzymes.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 6","pages":"559-565"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141330409","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":"Structure-Activity Relationship Study of CYM51010, an agonist for the µ-δ Opioid Receptor Heterodimer.","authors":"Ayaka Watanabe, Shuma Yamada, Haruka Yoshida, Miku Inagaki, Nao Atsumi, Aoba Matsushima, Naoki Takahashi, Naoto Ishibashi, Takumi Ogino, Ryoto Someya, Ai Taguchi, Ryo Kagaya, Karin Ashizawa, Hinako Mendori, Yusuke Karasawa, Kaori Ohshima, Akinobu Yokoyama, Miki Nonaka, Kanako Miyano, Fumika Karaki, Shigeto Hirayama, Kennosuke Itoh, Yasuhito Uezono, Hideaki Fujii","doi":"10.1248/cpb.c24-00188","DOIUrl":"https://doi.org/10.1248/cpb.c24-00188","url":null,"abstract":"<p><p>Although opioid analgesics are indispensable in treating pain, these drugs are accompanied by life-threatening side effects. While clinically relevant opioid drugs target the µ opioid receptor (MOR), a heterodimer between the MOR and the δ opioid receptor (DOR) has emerged as another target to develop safer analgesics. Although some heterodimer-preferring agonists have been reported so far, it is still difficult to activate the MOR/DOR heterodimer selectively in the presence of MOR or DOR monomers/homodimers. To gain insights to develop selective agonists for MOR/DOR, herein we prepared analogs of CYM51010, one of the reported heterodimer-preferring agonists, and collected structure-activity relationship information. We found that the ethoxycarbonyl group was needed for the activity for the heterodimer, although this group could be substituted with functional groups with similar sizes, such as an ethoxycarbonyl group. As for the acetylaminophenyl group, not a type of substituent, but rather a substituent located at a specific position (para-position) was essential for the activity. Changing the linker length between the acetylaminophenyl group and the piperidine moiety also had deleterious effects on the activity. On the other hand, the substitution of the acetylamino group with a trifluoroacetylamino group and the substitution of the phenethyl group with a benzyl group diminished the activities for the monomers/homodimers while keeping the activity for MOR/DOR, which enhanced the selectivity. Our findings herein will play an important role in developing selective agonists for MOR/DOR and for elucidating the physiological roles of this heterodimer in analgesic processes and in the establishment of side effects.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 7","pages":"711-730"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141859148","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":"Estimation for Raw Material Plants of a Henna Product Using LC-High Resolution MS and Multivariate Analysis.","authors":"Naohiro Oshima, Maiko Tahara, Tsuyoshi Kawakami, Akiko Yagami, Takumi Akiyama, Nahoko Uchiyama, Yoshiaki Ikarashi","doi":"10.1248/cpb.c24-00278","DOIUrl":"https://doi.org/10.1248/cpb.c24-00278","url":null,"abstract":"<p><p>Henna is a plant-based dye obtained from the powdered leaf of the pigmented plant Lawsonia inermis, and has often been used for grey hair dyeing, treatment, and body painting. As a henna product, the leaves of Indigofera tinctoria and Cassia auriculata can be blended to produce different colour variations. Although allergy from henna products attributed to p-phenylenediamine, which is added to enhance the dye, is reported occasionally, raw material plants of henna products could also contribute to the allergy. In this study, we reported that raw material plants of commercial henna products distributed in Japan can be estimated by LC-high resolution MS (LC-HRMS) and multivariate analysis. Principal Component Analysis (PCA) score plot clearly separated 17 samples into three groups [I; henna, II; blended henna primarily comprising Indigofera tinctoria, III; Cassia auriculata]. This grouping was consistent with the ingredient lists of products except that one sample listed as henna was classified as Group III, indicating that its ingredient label may differ from the actual formulation. The ingredients characteristic to Groups I, II, and III by PCA were lawsone (1), indirubin (2), and rutin (3), respectively, which were reported to be contained in each plant as ingredients. Therefore, henna products can be considered to have been manufactured from these plants. This study is the first to estimate raw material plants used in commercial plant-based dye by LC-HRMS and multivariate analysis.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 7","pages":"664-668"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141579057","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 the Factors Affecting the Patient-Centric Usability of Blister Packs for Spherical Capsules.","authors":"Kazuya Sugimoto, Hiromasa Uchiyama, Kazunori Kadota, Ken Yuki, Yuichi Tozuka","doi":"10.1248/cpb.c24-00572","DOIUrl":"https://doi.org/10.1248/cpb.c24-00572","url":null,"abstract":"<p><p>Pharmaceutical packaging is essential for enhancing the storage stability of medicine and can improve medication adherence and usability. Despite their widespread use, blister packs can be challenging to use, especially when pushing out the medication. This study investigates how specific cavity characteristics of blister packs can enhance usability for spherical capsules, which are harder to push out than tablets. The findings of this study show that reducing the thickness of the unformed sheet, or the thickness at the top and corners of the cavities, reduces the effort required to push out the capsules. Similarly, for cavities with different shapes, reducing the thickness at the top and increasing the corner radius also eases the push-out process. These insights emphasize the importance of systematic design in pharmaceutical packaging to improve patient medication adherence.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 12","pages":"1048-1054"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142779512","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":"Correlation between Membrane Permeability and the Intracellular Degradation Activity of Proteolysis-Targeting Chimeras.","authors":"Hidetomo Yokoo, Hinata Osawa, Kosuke Saito, Yosuke Demizu","doi":"10.1248/cpb.c24-00615","DOIUrl":"https://doi.org/10.1248/cpb.c24-00615","url":null,"abstract":"<p><p>Proteolysis-targeting chimeras (PROTACs) have attracted attention as an innovative drug modality that induces the selective degradation of target proteins. This technology shows higher activity than conventional inhibitors and holds great potential in the field of drug discovery. Optimization of the linker is essential for PROTACs to achieve sufficient activity, particularly with regard to cell membrane permeability. However, the correlation between membrane permeability and the activity of PROTACs has not been fully explored. To address this, we established a new molecular design approach to remove the linker and optimize PROTAC structure. These PROTAC compound groups were used to analyze the correlation between membrane permeability and activity using LC-tandem mass spectrometry (LC-MS/MS). Results revealed that the degradation activity of PROTACs fluctuates with increasing membrane permeability and changes in response to linker optimization, while sufficient proteolytic activity can be retained. These findings demonstrate the importance of considering the balance between membrane permeability and activity in PROTAC design and provide a new strategy for developing more effective PROTACs.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 11","pages":"961-965"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142615772","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":"Eperisone Hydrochloride, a Muscle Relaxant, Is a Potent P2X7 Receptor Antagonist.","authors":"Makoto Okada, Takashi Nose","doi":"10.1248/cpb.c24-00032","DOIUrl":"10.1248/cpb.c24-00032","url":null,"abstract":"<p><p>Eperisone Hydrochloride was launched in Japan in 1983 and has been used to improve muscle tone and treat spastic paralysis (Originator: Eisai Co., Ltd.). However, its biochemical mechanism of action is unknown. SB Drug Discovery was used to evaluate purinergic P2X (P2X) receptor antagonism using fluorescence. In this study, we discovered that its target protein is the P2X7 receptor. Also, P2X receptor subtype selectivity was high. This finding demonstrates the (Eperisone-P2X7-pain linkage), the validity of P2X7 as a drug target, and the possibility of drug repositioning of Eperisone Hydrochloride.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 3","pages":"345-348"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331559","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":"Nucleophilic Deprotection of p-Methoxybenzyl Ethers Using Heterogeneous Oxovanadium Catalyst.","authors":"Rei Ikeda, Tomoya Nishio, Kyohei Kanomata, Shuji Akai","doi":"10.1248/cpb.c23-00897","DOIUrl":"https://doi.org/10.1248/cpb.c23-00897","url":null,"abstract":"<p><p>Nucleophilic deprotection of p-methoxybenzyl (PMB) [p-methoxyphenylmethyl (MPM)] ethers was developed using a heterogeneous oxovanadium catalyst V-MPS4 and a thiol nucleophile. The deprotection method had a wide reaction scope, including PMB ethers of primary, secondary, and tertiary alcohols bearing various functional groups. In addition, the PMB ether of an oxidation-labile natural product was successfully removed by V-MPS4 catalysis, while a common oxidative method of PMB deprotection afforded a complex mixture. The V-MPS4 catalyst was reusable up to six times without a significant loss in the product yield. The advantages of using the heterogeneous catalyst were further demonstrated by conducting the deprotection reaction in a continuous flow process, which resulted in a 2.7-fold higher catalyst turnover number and 60-fold higher turnover frequency compared to those of the corresponding batch reaction.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 2","pages":"213-219"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139930255","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":"Controlled Release of Lysozyme Using Polyvinyl Alcohol-Based Polymeric Nanofibers Generated by Electrospinning.","authors":"Riho Ogawa, Kouji Hara, Ayaka Kobayashi, Nobuyoshi Yoshimura, Yutaka Taniguchi, Eriko Yamazoe, Takaaki Ito, Kohei Tahara","doi":"10.1248/cpb.c24-00024","DOIUrl":"10.1248/cpb.c24-00024","url":null,"abstract":"<p><p>Polymeric nanofibers generated via electrospinning offer a promising platform for drug delivery systems. This study examines the application of electrospun polyvinyl alcohol (PVA) nanofibers for controlled lysozyme (LZM) delivery. By using various PVA grades, such as the degree of polymerization/hydrolysis, this study investigates their influence on nanofiber morphology and drug-release characteristics. LZM-loaded PVA monolithic nanofibers having 50% drug content exhibit efficient entrapment, wherein rapid dissolution is achieved within 30 min. The initial burst of LZM from the nanofiber was reduced as the LZM content was lowered. The initial dissolution is greatly influenced by the choice of PVA grade used; fully hydrolyzed PVA nanofibers demonstrate controlled release due to the reduced water solubility of PVA. Furthermore, coaxial electrospinning, which creates core-shell nanofibers with polycaprolactone as a controlled release layer, enables sustained LZM release over an extended period. This study confirms a correlation between PVA characteristics and controlled drug release and provides valuable insights into tailoring nanofiber properties for pharmaceutical applications.</p>","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":"72 3","pages":"324-329"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140173893","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}