Chemical & pharmaceutical bulletin最新文献_第2页

Substrate Flexibilities of Norbelladine Synthase and Noroxomaritidine/Norcraugsodine Reductase for Hydroxylated and/or Methoxylated Aldehydes Norbelladine 合成酶和 Noroxomaritidine/Norcraugsodine 还原酶对羟基化和/或甲氧基化醛的底物灵活性

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-05-28 DOI: 10.1248/cpb.c24-00174

Saw Yu Yu Hnin, Yu Nakashima, Hiroyuki Morita

{"title":"Substrate Flexibilities of Norbelladine Synthase and Noroxomaritidine/Norcraugsodine Reductase for Hydroxylated and/or Methoxylated Aldehydes","authors":"Saw Yu Yu Hnin, Yu Nakashima, Hiroyuki Morita","doi":"10.1248/cpb.c24-00174","DOIUrl":"https://doi.org/10.1248/cpb.c24-00174","url":null,"abstract":"Amaryllidaceae alkaloids are structurally diverse natural products with a wide range biological properties, and based on the partial identification of the biosynthetic enzymes, norbelladine would be a common intermediate in the biosynthetic pathways. Previous studies suggested that norbelladine synthase (NBS) catalyzed the condensation reaction of 3,4-dihydroxybenzaldehyde and tyramine to form norcraugsodine, and subsequently, noroxomaritidine/norcraugsodine reductase (NR) catalyzed the nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reduction of norcraugsodine to generate norbelladine. However, recent studies have highlighted possible alternative Amaryllidaceae alkaloid biosynthetic pathways via the formation of isovanillin and vanillin from the 4-O- and 3-O-methylation reactions of 3,4-dihydroxybenzaldehyde, respectively. Herein, we focused on NpsNBS and NpsNR, which were initially identified from Narcissus pseudonarcissus, and explored their substrate recognition tolerance by performing condensation reactions of tyramine with various benzaldehyde derivatives, to shed light on the Amaryllidaceae alkaloid biosynthetic pathway from the viewpoint of the enzymatic properties. The assays revealed that both NpsNBS and NpsNR lacked the abilities to produce 4′-O- and 3′-O-methylnorbelladine from isovanillin and vanillin with tyramine, respectively. These observations thus suggested that Amaryllidaceae alkaloids are biosynthesized from norbelladine, formed through the condensation/reduction reaction of 3,4-dihydroxybenzaldehyde with tyramine.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/5/72_c24-00174/figure/72_c24-00174.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141165749","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

Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents. 作为抗癌剂的两种对映体纯蜕皮素衍生物的合成、抗增殖活性和分子对接分析

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-05-25 Epub Date: 2024-05-11 DOI: 10.1248/cpb.c23-00718

Junseong Ahn, Hyun-Ha Hwang, Soo Yeon Jung, Ja Yeon Lee, Choi Kim, Hye Min Choi, Min Ju Gwon, Min Ji Kim, Youngbin Kwon, Jaehyuk Woo, Bongkyu Park, Seong-Gyu Ko, Jae Yeol Lee

{"title":"Synthesis, Antiproliferative Activity and Molecular Docking Analysis of Both Enantiomerically Pure Decursin Derivatives as Anticancer Agents.","authors":"Junseong Ahn, Hyun-Ha Hwang, Soo Yeon Jung, Ja Yeon Lee, Choi Kim, Hye Min Choi, Min Ju Gwon, Min Ji Kim, Youngbin Kwon, Jaehyuk Woo, Bongkyu Park, Seong-Gyu Ko, Jae Yeol Lee","doi":"10.1248/cpb.c23-00718","DOIUrl":"10.1248/cpb.c23-00718","url":null,"abstract":"Using (S)-decursinol isolated from root of Angelica gigas Nakai (AGN), we semi-synthesized and evaluated a series of both enantiomerically pure decursin derivatives for their antiproliferative activities against A549 human lung cancer cells. All synthesized compounds showed a broad spectrum of inhibitory activities against the growth of A549 cells. Especially, compound (S)-2d with (E)-(furan-3-yl)acryloyl group showed the most potent activity (IC50: 14.03 µM) against A549 cancer cells as compared with the reference compound, decursin (IC50: 43.55 µM) and its enantiomer, (R)-2d (IC50: 151.59 µM). Western blotting assays indicated that (S)-2d more strongly inhibited Janus kinase 1 (JAK1) and signal transducer and activator of transcription activation 3 (STAT3) phosphorylation than decursin in a dose-dependent manner, while having no effect on CXCR7 overexpression and total STAT3 level. In addition, (S)-2d induced cell cycle arrest at G1 phase and subsequent apoptotic cell death in A549 cancer cells. Our combined analysis of molecular docking studies and biological data suggests that the inhibition of JAK1 with (S)-2d resulted in loss of STAT3 phosphorylation and inhibition of cell growth in A549 cancer cells. These overall results strongly suggest that (S)-2d (MRC-D-004) as a novel JAK1 inhibitor may have therapeutic potential in the treatment of A549 human lung cancers by targeting the JAK1/STAT3 signaling pathway.","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140910861","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

Studies on Comprehensive Total Synthesis of Natural and Pseudo-Natural Products for Drug Discovery 用于药物发现的天然和伪天然产品的综合全合成研究

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-05-01 DOI: 10.1248/cpb.c24-00056

Atsushi Nakayama

引用次数: 0

Development of Efficient Synthetic Reactions Using Enamines and Enamides Carrying Oxygen Atom Substituent on Nitrogen Atom 利用氮原子上带有氧原子取代基的烯胺和烯酰胺开发高效合成反应

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-05-01 DOI: 10.1248/cpb.c23-00915

Okiko Miyata

{"title":"Development of Efficient Synthetic Reactions Using Enamines and Enamides Carrying Oxygen Atom Substituent on Nitrogen Atom","authors":"Okiko Miyata","doi":"10.1248/cpb.c23-00915","DOIUrl":"https://doi.org/10.1248/cpb.c23-00915","url":null,"abstract":"We have developed efficient synthetic reactions using enamines and enamides carrying oxygen atom substituent on nitrogen, such as N-alkoxyenamines, N,α-dialkoxyenamines, N-alkoxyanamides, and N-(benzoyloxy)enamides. The umpolung reaction by polarity inversion at the β-position of N-alkoxyenamines afforded α-alkyl-, α-aryl-, α-alkenyl-, and α-heteroarylketones by using aluminum reagent as nucleophiles. Furthermore, one-pot umpolung α-phenylation of ketones has been also developed. We applied this method to umpolung reaction of N,α-dialkoxyenamine, generated from N-alkoxyamide to afford α-arylamides. The vicinal functionalization of N-alkoxyenamines has been achieved with the formation of two new carbon–carbon bonds by using an organo-aluminum reagent and subsequent allyl magnesium bromide or tributyltin cyanide. A sequential retro-ene arylation has been developed for the conversion of N-alkoxyenamides to the corresponding tert-alkylamines. The [3,3]-sigmatropic rearrangement of N-(benzoyloxy)enamides followed by arylation afforded cyclic β-aryl-β-amino alcohols bearing a tetrasubstituted carbon center. The resulting products were converted into the corresponding sterically congested cyclic β-amino alcohols, as well as the dissociative anesthetic agent Tiletamine.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/5/72_c23-00915/figure/72_c23-00915.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140834086","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

Effect of 1,4-Dioxane Solvent on β-Glucuronidation Using Methyl 1,2,3,4-Tetra-O-acetyl-β-D-glucuronate as the Glycosyl Donor. 以 1,2,3,4-O-四乙酰基-β-D-葡萄糖醛酸甲酯为糖基供体，1,4-二氧六环溶剂对β-葡萄糖醛酸化作用的影响

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-04-25 DOI: 10.1248/cpb.c24-00068

Tetsuya Kajimoto, Tianqi Du, Kimiyoshi Kaneko, Yasuyuki Matsushima, Tsuyoshi Miura

引用次数: 0

Discovery and Structure–Activity Relationship of a Ryanodine Receptor 2 Inhibitor Ryanodine 受体 2 抑制剂的发现与结构活性关系

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-04-22 DOI: 10.1248/cpb.c24-00114

Ryosuke Ishida, Xi Zeng, Nagomi Kurebayashi, Takashi Murayama, Shuichi Mori, Hiroyuki Kagechika

{"title":"Discovery and Structure–Activity Relationship of a Ryanodine Receptor 2 Inhibitor","authors":"Ryosuke Ishida, Xi Zeng, Nagomi Kurebayashi, Takashi Murayama, Shuichi Mori, Hiroyuki Kagechika","doi":"10.1248/cpb.c24-00114","DOIUrl":"https://doi.org/10.1248/cpb.c24-00114","url":null,"abstract":"Ryanodine receptor 2 (RyR2) is a large Ca2+-release channel in the sarcoplasmic reticulum (SR) of cardiac muscle cells. It serves to release Ca2+ from the SR into the cytosol to initiate muscle contraction. RyR2 overactivation is associated with arrhythmogenic cardiac disease, but few specific inhibitors have been reported so far. Here, we identified an RyR2-selective inhibitor 1 from the chemical compound library and synthesized it from glycolic acid. Synthesis of various derivatives to investigate the structure–activity relationship of each substructure afforded another two RyR2-selective inhibitors 6 and 7, among which 6 was the most potent. Notably, compound 6 also inhibited Ca2+ release in cells expressing the RyR2 mutants R2474S, R4497C and K4750Q, which are associated with cardiac arrhythmias such as catecholaminergic polymorphic ventricular tachycardia (CPVT). This inhibitor is expected to be a useful tool for research on the structure and dynamics of RyR2, as well as a lead compound for the development of drug candidates to treat RyR2-related cardiac disease.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/4/72_c24-00114/figure/72_c24-00114.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635889","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

In Vitro and in Vivo Study of a Photostable Quinone Compound with Enhanced Therapeutic Efficacy against Chagas Disease 具有增强南美锥虫病疗效的光稳定醌化合物的体外和体内研究

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-04-19 DOI: 10.1248/cpb.c24-00116

Yutaka Suto, Nagisa Inoue, Mohammed Suliman Omer Tagod, Yoko Onizuka, Tomoya Nobuta, Mayumi Ishii, Daniel Ken Inaoka, Kayoko Kanamitsu, Noriyuki Yamagiwa, Junko Nakajima-Shimada

{"title":"In Vitro and in Vivo Study of a Photostable Quinone Compound with Enhanced Therapeutic Efficacy against Chagas Disease","authors":"Yutaka Suto, Nagisa Inoue, Mohammed Suliman Omer Tagod, Yoko Onizuka, Tomoya Nobuta, Mayumi Ishii, Daniel Ken Inaoka, Kayoko Kanamitsu, Noriyuki Yamagiwa, Junko Nakajima-Shimada","doi":"10.1248/cpb.c24-00116","DOIUrl":"https://doi.org/10.1248/cpb.c24-00116","url":null,"abstract":"Chagas disease, a neglected tropical disease caused by the protozoan Trypanosoma cruzi poses a significant health challenge in rural areas of Latin America. The current pharmacological options exhibit notable side effects, demand prolonged administration, and display limited efficacy. Consequently, there is an urgent need to develop drugs that are safe and clinically effective. Previously, we identified a quinone compound (designated as compound 2) with potent antiprotozoal activity, based on the chemical structure of komaroviquinone, a natural product renowned for its antitrypanosomal effects. However, compound 2 was demonstrated considerably unstable to light. In this study, we elucidated the structure of the light-induced degradation products of compound 2 and probed the correlation between the quinone ring’s substituents and its susceptibility to light. Our findings led to the discovery of quinones with significantly enhanced light stability, some of which exhibiting antitrypanosomal activity. The most promising compound was evaluated for drug efficacy in a mouse model of Chagas disease, revealing where a notable reduction in blood parasitemia.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/4/72_c24-00116/figure/72_c24-00116.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627687","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

Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia Procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis 探究羧甲基化和交联白花蛇舌草胶在盐酸地尔硫卓基质片中的功效：对比分析

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-04-19 DOI: 10.1248/cpb.c23-00652

Sudipta Mukherjee, Jasmina Khanam

{"title":"Exploring the Effectiveness of Carboxymethylated and Crosslinked Albizia Procera Gum in Diltiazem Hydrochloride Matrix Tablets: A Comparative Analysis","authors":"Sudipta Mukherjee, Jasmina Khanam","doi":"10.1248/cpb.c23-00652","DOIUrl":"https://doi.org/10.1248/cpb.c23-00652","url":null,"abstract":"This study investigates the efficacy of modified Albizia procera gum as a release-retardant polymer in Diltiazem hydrochloride (DIL) matrix tablets. Carboxymethylated Albizia procera gum (CAP) and ionically crosslinked carboxymethylated Albizia procera gum (Ca-CAP) were utilized, with Ca-CAP synthesized via crosslinking CAP with calcium ions (Ca2+) using calcium chloride (CaCl2). FTIR analysis affirmed polymer compatibility, while Differential scanning calorimetry (DSC) and X-ray diffraction (XRD) assessed thermal behavior and crystallinity, respectively. Zeta potential analysis explored surface charge and electrostatic interactions, while rheology examined flow and viscoelastic properties. Swelling and erosion kinetics provided insights into water penetration and stability. CAP's carboxymethyl groups (-CH2-COO-) heightened divalent cation reactivity, and crosslinking with CaCl2 produced Ca-CAP through -CH2-COO- and Ca2+ interactions. Structural similarities between the polymers were revealed by FTIR, with slight differences. DSC indicated modified thermal behavior in Ca-CAP, while Zeta potential analysis showcased negative charges, with Ca-CAP exhibiting lower negativity. XRD highlighted increased crystallinity in Ca-CAP due to calcium crosslinking. Minimal impact on RBC properties was observed with both polymers compared to the positive control as water for injection (WFI). Ca-CAP exhibited improved viscosity, strength, controlled swelling, and erosion, allowing prolonged drug release compared to CAP. Stability studies confirmed consistent six-month drug release, emphasizing Ca-CAP's potential as a stable, sustained drug delivery system over CAP. Robustness and accelerated stability tests supported these findings, underscoring the promise of Ca-CAP in controlled drug release applications.\u0000","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140627388","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

Discovery of a Novel Lidocaine Metabolite by Human Liver Microsome and Identification of Microbial Species Which Produces the Same Metabolite 人肝微粒体发现新型利多卡因代谢物并鉴定产生相同代谢物的微生物物种

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-04-19 DOI: 10.1248/cpb.c24-00050

Sho Hori, Hikari Taniguchi, Sota Yoshimura, Kanako Takeda, Ryusei Yamashita, Atsushi Kimishima, Kazuo Harada

{"title":"Discovery of a Novel Lidocaine Metabolite by Human Liver Microsome and Identification of Microbial Species Which Produces the Same Metabolite","authors":"Sho Hori, Hikari Taniguchi, Sota Yoshimura, Kanako Takeda, Ryusei Yamashita, Atsushi Kimishima, Kazuo Harada","doi":"10.1248/cpb.c24-00050","DOIUrl":"https://doi.org/10.1248/cpb.c24-00050","url":null,"abstract":"Preparation of drug metabolites at the milligram scale is essential for determining the structure and toxicity of drug metabolites. However, their preparation using recombinant proteins and human liver microsomes (HLM) is often difficult because of technical and ethical issues. Reproducing human drug metabolism in food-derived microorganisms may be useful for overcoming these challenges. In this study, we identified an unknown metabolite of the anaesthetic drug lidocaine, which is metabolised by HLM. By screening for lidocaine metabolic activity in five types of foods (blue cheese, shiitake mushroom, natto, yoghurt, and dry yeast), we found that bacteria isolated from natto reproduced the lidocaine metabolic reaction that occurs in HLM. A fraction containing the unknown lidocaine metabolite was prepared through mass cultivation of a Bacillus subtilis standard strain, ethyl acetate extraction, open column chromatography, and HPLC purification. We identified the unknown metabolite as 3-(2,6-dimethylphenyl)-1-ethyl-2-methyl-4-imidazolidinone using NMR. Our results showed that food-derived microorganisms can produce large amounts of human drug metabolites via large-scale cultivation. Additionally, food microorganisms that can reproduce drug metabolism in humans can be used to examine drug metabolites at a low cost and without ethical issues.\u0000\u0000<img alt=\"\" src=\"https://www.jstage.jst.go.jp/pub/cpb/72/4/72_c24-00050/figure/72_c24-00050.png\"/>\u0000Fullsize Image","PeriodicalId":9773,"journal":{"name":"Chemical & pharmaceutical bulletin","volume":null,"pages":null},"PeriodicalIF":1.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140630424","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

Comparison of Non-ephedrine Constituents from Ephedra Plants Cultivated in Japan 日本种植的麻黄属植物中的非麻黄碱成分比较

IF 1.7 4区医学

Chemical & pharmaceutical bulletin Pub Date : 2024-04-17 DOI: 10.1248/cpb.c24-00043

Kengo Hayashi, Yuki Miyao, Hina Matsui, Takao Yamaura, Ken Tanaka, Mariko Baba, Hiroaki Hayashi

引用次数: 0