Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00151-F
Nahoko Uchiyama, Naoki Sugimoto
{"title":"[Implementation and Future of Quantitative NMR in the Pharmaceutical and Food Fields].","authors":"Nahoko Uchiyama, Naoki Sugimoto","doi":"10.1248/yakushi.23-00151-F","DOIUrl":"10.1248/yakushi.23-00151-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140332007","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.24-00031
Atsushi Mitsumoto, Tohru Yamazaki
Recently, feeding damage by the olive weevil Pimelocerus (Dyscerus) perforatus Roelofs, which utilizes olive trees (Olea europaea Linne) as a host plant, has become the biggest obstacle to olive cultivation in Japan. We previously identified several volatile plant-derived natural products that exhibit repellent activity against olive weevils. In this study, we conducted a pilot test of repellents in an olive orchard along with the use of insecticide. During three consecutive years from 2021 to 2023, the first year was the observation period, and the second and third years were set aside for a trial period for o-vanillin and geraniol as repellents, respectively. Using o-vanillin, the number of adult olive weevil outbreaks decreased to almost half a year in the experimental area, the use of geraniol then resulted in a drastic reduction of the number of individual olive weevils in the experimental area. In contrast, adults and larvae outbreaks increased in the control area without a repellent, despite the use of insecticide. These results indicate that the volatile repellents drove the olive weevils away and kept them at bay in the field. Based on the observations, we will be able to provide a new approach for the control of olive cultivation, including fruit and leaves used for commercial purposes, following integrated pest management (IPM) practices, such as reducing environmental poisoning from intense insecticides, and returning olive weevils to their original habitat outside of olive orchards.
{"title":"[A Pilot Test of Olive Weevil Repellents in an Olive Orchard].","authors":"Atsushi Mitsumoto, Tohru Yamazaki","doi":"10.1248/yakushi.24-00031","DOIUrl":"10.1248/yakushi.24-00031","url":null,"abstract":"<p><p>Recently, feeding damage by the olive weevil Pimelocerus (Dyscerus) perforatus Roelofs, which utilizes olive trees (Olea europaea Linne) as a host plant, has become the biggest obstacle to olive cultivation in Japan. We previously identified several volatile plant-derived natural products that exhibit repellent activity against olive weevils. In this study, we conducted a pilot test of repellents in an olive orchard along with the use of insecticide. During three consecutive years from 2021 to 2023, the first year was the observation period, and the second and third years were set aside for a trial period for o-vanillin and geraniol as repellents, respectively. Using o-vanillin, the number of adult olive weevil outbreaks decreased to almost half a year in the experimental area, the use of geraniol then resulted in a drastic reduction of the number of individual olive weevils in the experimental area. In contrast, adults and larvae outbreaks increased in the control area without a repellent, despite the use of insecticide. These results indicate that the volatile repellents drove the olive weevils away and kept them at bay in the field. Based on the observations, we will be able to provide a new approach for the control of olive cultivation, including fruit and leaves used for commercial purposes, following integrated pest management (IPM) practices, such as reducing environmental poisoning from intense insecticides, and returning olive weevils to their original habitat outside of olive orchards.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141200640","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00170
Takashi Tanaka
Tannins are a group of polyphenols that possess the ability to precipitate proteins, causing an undesirable astringent taste by interacting with salivary peptides. This interaction deactivates the digestive enzymes; therefore, tannins are considered as plant defense substances. The health benefits of tannins and related polyphenols in foods and beverages have been demonstrated by biological and epidemiological studies; however, their metabolism in living plants and the chemical changes observed during processing of foods and medicinal herbs raises some questions. This review summarizes our studies concerning dynamic changes observed in tannins. Ellagitannins present in the young leaves of Camellia japonica and Quercus glauca undergo oxidative degradation as the leaves mature. Similar oxidative degradation is also observed in whiskey when it is kept for aging in oak barrels, and in decaying wood caused by fungi in natural forests. In contrast, ellagitannins have been observed to undergo reduction in the leaves of Carpinus, Castanopsis, and Triadica species as the leaves mature. This phenomenon of reductive metabolism in leaves enabled us to propose a new biosynthetic pathway for the most fundamental ellagitannin acyl groups, which was also supported by biomimetic synthetic studies. Polyphenols undergo dynamic changes during the process of food processing. Catechin in tea leaves undergo oxidation upon mechanical crushing to generate black tea polyphenols. Though detailed production mechanisms of catechin dimers have been elucidated, structures of thearubigins (TRs), which are complex mixtures of oligomers, remain ambiguous. Our recent studies suggested that catechin B-ring quinones couple with catechin A-rings during the process of oligomerization.
单宁酸是一类多酚类物质,具有沉淀蛋白质的能力,通过与唾液肽相互作用,产生一种不良的涩味。这种相互作用会使消化酶失活,因此单宁酸被视为植物防御物质。生物学和流行病学研究证明,食品和饮料中的单宁酸和相关多酚对健康有益;然而,单宁酸在活体植物中的新陈代谢以及在食品和药材加工过程中观察到的化学变化提出了一些问题。本综述总结了我们对单宁酸动态变化的研究。山茶和柞树嫩叶中的鞣花丹宁会随着叶子的成熟而发生氧化降解。威士忌在橡木桶中陈酿时也会发生类似的氧化降解,天然森林中的真菌也会导致木材腐烂。与此相反,人们观察到鞣花丹宁会随着木犀属(Carpinus)、栲属(Castanopsis)和三叶草属(Triadica)物种叶子的成熟而减少。叶片中的这种还原代谢现象使我们能够为最基本的鞣花丹宁酰基提出一种新的生物合成途径,生物模拟合成研究也支持这一观点。多酚在食品加工过程中会发生动态变化。茶叶中的儿茶素在机械粉碎时会发生氧化,生成红茶多酚。虽然儿茶素二聚体的详细生成机制已被阐明,但由低聚物组成的复杂混合物大黄素(TRs)的结构仍然模糊不清。我们最近的研究表明,在低聚物形成过程中,儿茶素 B 环醌与儿茶素 A 环发生了耦合。
{"title":"[Dynamic Chemistry of Tannins].","authors":"Takashi Tanaka","doi":"10.1248/yakushi.23-00170","DOIUrl":"10.1248/yakushi.23-00170","url":null,"abstract":"<p><p>Tannins are a group of polyphenols that possess the ability to precipitate proteins, causing an undesirable astringent taste by interacting with salivary peptides. This interaction deactivates the digestive enzymes; therefore, tannins are considered as plant defense substances. The health benefits of tannins and related polyphenols in foods and beverages have been demonstrated by biological and epidemiological studies; however, their metabolism in living plants and the chemical changes observed during processing of foods and medicinal herbs raises some questions. This review summarizes our studies concerning dynamic changes observed in tannins. Ellagitannins present in the young leaves of Camellia japonica and Quercus glauca undergo oxidative degradation as the leaves mature. Similar oxidative degradation is also observed in whiskey when it is kept for aging in oak barrels, and in decaying wood caused by fungi in natural forests. In contrast, ellagitannins have been observed to undergo reduction in the leaves of Carpinus, Castanopsis, and Triadica species as the leaves mature. This phenomenon of reductive metabolism in leaves enabled us to propose a new biosynthetic pathway for the most fundamental ellagitannin acyl groups, which was also supported by biomimetic synthetic studies. Polyphenols undergo dynamic changes during the process of food processing. Catechin in tea leaves undergo oxidation upon mechanical crushing to generate black tea polyphenols. Though detailed production mechanisms of catechin dimers have been elucidated, structures of thearubigins (TRs), which are complex mixtures of oligomers, remain ambiguous. Our recent studies suggested that catechin B-ring quinones couple with catechin A-rings during the process of oligomerization.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139698430","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}
A 65-years-old man undergoing hemodialysis for chronic kidney disease was diagnosed with ascending colon cancer and 3 hepatic metastases. He was administered mFOLFOX6 (reducing the dose to 50%) plus bevacizumab (BEV) therapy. Hemodialysis was performed 4 h after administration of oxaliplatin on day1 and repeated three times a week. No serious adverse events were observed. After 4 courses of chemotherapy, a computer tomography scan showed that the hepatic metastases had reduced. 2 courses of mFOLFOX6 (increasing the dose to 75%) plus BEV therapy were added, he was operated by laparoscopic right hemicolectomy and laparoscopic patrial hepatectomy. He has been in remission for 2 years and 4 months since the surgery. Dose-adjusted chemotherapy with hemodialysis was effective and improve the prognosis of the patient.
{"title":"[A Case Report of Successful Treatment with Dose-controlled mFOFOX6+Bevacizumab for Metastatic Colorectal Cancer in Patient Receiving Hemodialysis].","authors":"Ayumi Ozeki, Hideya Kokubun, Sho Ibuki, Masayuki Inamoto, Yoshihiko Sakurai, Takahiro Otani, Junya Sato","doi":"10.1248/yakushi.24-00004","DOIUrl":"https://doi.org/10.1248/yakushi.24-00004","url":null,"abstract":"<p><p>A 65-years-old man undergoing hemodialysis for chronic kidney disease was diagnosed with ascending colon cancer and 3 hepatic metastases. He was administered mFOLFOX6 (reducing the dose to 50%) plus bevacizumab (BEV) therapy. Hemodialysis was performed 4 h after administration of oxaliplatin on day1 and repeated three times a week. No serious adverse events were observed. After 4 courses of chemotherapy, a computer tomography scan showed that the hepatic metastases had reduced. 2 courses of mFOLFOX6 (increasing the dose to 75%) plus BEV therapy were added, he was operated by laparoscopic right hemicolectomy and laparoscopic patrial hepatectomy. He has been in remission for 2 years and 4 months since the surgery. Dose-adjusted chemotherapy with hemodialysis was effective and improve the prognosis of the patient.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141861084","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.24-00127
Yoshiaki Kariya
Biological systems are complex, and although researchers strive to understand them, the accumulated knowledge often complicates integrative comprehension. Consolidating this knowledge can provide insights into the landscape of specific biological events. Our study on bone metabolism, focusing on the behavior of the receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) highlighted the challenges in understanding its role across different cell types. At the same time, the study underscores the importance of exploring interactions between various players (cell types and genes/proteins) in complex systems, which is a core focus of systems biology. Analysis by mathematical models is a potentially powerful tool for describing the dynamic behavior of components in the interaction networks. However, such model-based analyses are limited by parameter availability and reliability. To address this, we proposed two approaches, i.e., sequential simulation and system-wide behavior constraints. Sequential simulation of small dynamic models offers potential in reproducing behavior in larger networks, as seen in toxicity analysis of sunitinib-related adverse effects. System-wide constraints derived from "homeostasis" help reduce the parameter search space in large-scale models, as demonstrated in model-based analysis of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the arachidonic acid pathway. These analytical approaches offer insights into biological system dynamics and can enhance our understanding of pharmacological effects that result from perturbations in complexities of biological systems.
{"title":"[Challenges in Understanding the Biological and Pharmacological Responses Based on Emergent Complexity in Biological Systems: From Bone Metabolism to General Physiology].","authors":"Yoshiaki Kariya","doi":"10.1248/yakushi.24-00127","DOIUrl":"https://doi.org/10.1248/yakushi.24-00127","url":null,"abstract":"<p><p>Biological systems are complex, and although researchers strive to understand them, the accumulated knowledge often complicates integrative comprehension. Consolidating this knowledge can provide insights into the landscape of specific biological events. Our study on bone metabolism, focusing on the behavior of the receptor activator of nuclear factor kappa B (RANK) and its ligand (RANKL) highlighted the challenges in understanding its role across different cell types. At the same time, the study underscores the importance of exploring interactions between various players (cell types and genes/proteins) in complex systems, which is a core focus of systems biology. Analysis by mathematical models is a potentially powerful tool for describing the dynamic behavior of components in the interaction networks. However, such model-based analyses are limited by parameter availability and reliability. To address this, we proposed two approaches, i.e., sequential simulation and system-wide behavior constraints. Sequential simulation of small dynamic models offers potential in reproducing behavior in larger networks, as seen in toxicity analysis of sunitinib-related adverse effects. System-wide constraints derived from \"homeostasis\" help reduce the parameter search space in large-scale models, as demonstrated in model-based analysis of the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on the arachidonic acid pathway. These analytical approaches offer insights into biological system dynamics and can enhance our understanding of pharmacological effects that result from perturbations in complexities of biological systems.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112718","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.24-00117
Yuta Ito
Nucleosides with a substituent at the 4'-position have received much attention as antiviral drugs and as raw materials for oligonucleotide therapeutics. 4'-Modified nucleosides are generally synthesized using ionic reactions through the introduction of electrophilic or nucleophilic substituents at the 4'-position. However, their synthetic methods have some drawbacks; e.g., (i) it is difficult to control stereoselectivity at the 4'-position; (ii) complex protection-deprotection processes are required; (iii) the range of electrophiles and nucleophiles is limited. With this background, we considered that a carbon radical generated at the 4'-position would be a useful intermediate for the synthesis of 4'-modified nucleosides. In this review, two novel methods for the generation of 4'-carbon radicals are summarized. The first utilizes radical deformylation involving β-fragmentation of a hydroxymethyl group at the 4'-position. The other utilizes radical decarboxylation and 1,5-hydrogen atom transfer (1,5-HAT), which enables the generation of 4'-carbon radicals while retaining the hydroxymethyl group at the 4'-position. These methods enable the rapid and facile generation of 4'-carbon radicals and provide various 4'-modified nucleosides including 2',4'-bridged structures.
{"title":"[Synthesis of Modified Nucleosides Using 4'-Carbon Radicals].","authors":"Yuta Ito","doi":"10.1248/yakushi.24-00117","DOIUrl":"https://doi.org/10.1248/yakushi.24-00117","url":null,"abstract":"<p><p>Nucleosides with a substituent at the 4'-position have received much attention as antiviral drugs and as raw materials for oligonucleotide therapeutics. 4'-Modified nucleosides are generally synthesized using ionic reactions through the introduction of electrophilic or nucleophilic substituents at the 4'-position. However, their synthetic methods have some drawbacks; e.g., (i) it is difficult to control stereoselectivity at the 4'-position; (ii) complex protection-deprotection processes are required; (iii) the range of electrophiles and nucleophiles is limited. With this background, we considered that a carbon radical generated at the 4'-position would be a useful intermediate for the synthesis of 4'-modified nucleosides. In this review, two novel methods for the generation of 4'-carbon radicals are summarized. The first utilizes radical deformylation involving β-fragmentation of a hydroxymethyl group at the 4'-position. The other utilizes radical decarboxylation and 1,5-hydrogen atom transfer (1,5-HAT), which enables the generation of 4'-carbon radicals while retaining the hydroxymethyl group at the 4'-position. These methods enable the rapid and facile generation of 4'-carbon radicals and provide various 4'-modified nucleosides including 2',4'-bridged structures.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112723","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00153
Takahide Nishi
After graduating with a master's degree from Faculty of Pharmaceutical Sciences, Hokkaido University in 1983, I worked in medicinal chemistry for 37 years at a pharmaceutical company and 4 years at a university. On this occasion of my retirement, I would like to summarize the memorable reactions from my life in research over more than 40 years. This includes an overview of my drug discovery research at pharmaceutical companies covering practical and effective synthetic methods of key intermediates for renin inhibitors, 1β-methylcarbapenem, neurokinin receptor antagonists and sphingosine-1-phosphate receptor agonists. I have also described microbial transformation reactions for phosphorylation and glucuronidation, as well as antibacterial cyclic peptide and ogipeptins. During this time, two years of studying at the Scripps Research Institute and three years of working in India were also very valuable experiences. Finally, I have summarized the results of synthetic research on indole and azaindole derivatives conducted at the Health Sciences University of Hokkaido over a period of four years.
{"title":"[Looking Back on My Life in Research over more than 40 Years].","authors":"Takahide Nishi","doi":"10.1248/yakushi.23-00153","DOIUrl":"10.1248/yakushi.23-00153","url":null,"abstract":"<p><p>After graduating with a master's degree from Faculty of Pharmaceutical Sciences, Hokkaido University in 1983, I worked in medicinal chemistry for 37 years at a pharmaceutical company and 4 years at a university. On this occasion of my retirement, I would like to summarize the memorable reactions from my life in research over more than 40 years. This includes an overview of my drug discovery research at pharmaceutical companies covering practical and effective synthetic methods of key intermediates for renin inhibitors, 1β-methylcarbapenem, neurokinin receptor antagonists and sphingosine-1-phosphate receptor agonists. I have also described microbial transformation reactions for phosphorylation and glucuronidation, as well as antibacterial cyclic peptide and ogipeptins. During this time, two years of studying at the Scripps Research Institute and three years of working in India were also very valuable experiences. Finally, I have summarized the results of synthetic research on indole and azaindole derivatives conducted at the Health Sciences University of Hokkaido over a period of four years.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088703","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00162-F
Kazuhiro Nishiyama, Takashi Toyama
{"title":"[Supersulfides in Environmental Toxicology and Hygiene].","authors":"Kazuhiro Nishiyama, Takashi Toyama","doi":"10.1248/yakushi.23-00162-F","DOIUrl":"10.1248/yakushi.23-00162-F","url":null,"abstract":"","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088707","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.23-00161-2
Tatsufumi Okino
More than 2000 compounds have been reported from cyanobacteria. The most successful example is dolastatin 10, of which a related compound monomethylauristatin E is used as antibody-drug conjugate (ADC) for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Recently genome-based analyses by Piel led to the discovery of novel compounds from cyanobacteria. W. H. Gerwick found a potential as anti-SARS-CoV-2 agent in gallinamide A, which was reported as a cathepsin L inhibitor. In our group columbamides were isolated from the marine cyanobacterium Moorena bouillonii. The geometry of the double bond was determined by the coupling constant obtained using non-decoupled heteronuclear single quantum coherence (HSQC). The configuration of chloromethine in a long-chain acyl moiety was determined by the Ohrui method at room temperature using a chiral HPLC column. Columbamide D showed biosurfactant activity. One strain many compounds (OSMAC) is a method to discover new compounds by changing culture conditions. Prior to our experiments, attempts to apply OSMAC in cyanobacteria resulted in the induction or up-regulation of only known compounds. The heat shock culture of the freshwater cyanobacterium Microcystis aeruginosa up-regulated a ribosomal peptide argicyclamide C. At the same time, we discovered bis-prenylated and monoprenylated argicyclamides A and B. More recently iron-limited culture produced hydroxylated argicyclamide A. OSMAC and genome-based screening could lead the discovery of unique biologically active compounds from cyanobacteria.
据报道,蓝藻中含有 2000 多种化合物。其中最成功的例子是多拉他汀 10,其相关化合物单甲基金丝桃素 E 被用作治疗霍奇金淋巴瘤和全身性无性大细胞淋巴瘤的抗体药物结合剂(ADC)。最近,Piel 基于基因组的分析发现了蓝藻中的新型化合物。W. H. Gerwick 发现五倍子酰胺 A 具有抗 SARS-CoV-2 的潜力,据报道它是一种酪蛋白酶 L 抑制剂。我们的研究小组从海洋蓝藻 Moorena bouillonii 中分离出了胆酰胺。双键的几何形状是通过使用非去耦异核单量子相干(HSQC)获得的耦合常数确定的。长链酰基中氯甲基的构型是在室温下利用手性高效液相色谱柱通过 Ohrui 法确定的。哥伦酰胺 D 具有生物表面活性剂活性。一株多化合物(OSMAC)是一种通过改变培养条件发现新化合物的方法。在我们的实验之前,尝试在蓝藻中应用 OSMAC 的结果只是诱导或上调了已知化合物。淡水蓝藻铜绿微囊藻(Microcystis aeruginosa)的热休克培养上调了核糖体肽水杨酰胺 C。OSMAC 和基于基因组的筛选可帮助我们从蓝藻中发现独特的生物活性化合物。
{"title":"[Up to Date of Cyanobacterial Natural Products].","authors":"Tatsufumi Okino","doi":"10.1248/yakushi.23-00161-2","DOIUrl":"10.1248/yakushi.23-00161-2","url":null,"abstract":"<p><p>More than 2000 compounds have been reported from cyanobacteria. The most successful example is dolastatin 10, of which a related compound monomethylauristatin E is used as antibody-drug conjugate (ADC) for Hodgkin lymphoma and systemic anaplastic large cell lymphoma. Recently genome-based analyses by Piel led to the discovery of novel compounds from cyanobacteria. W. H. Gerwick found a potential as anti-SARS-CoV-2 agent in gallinamide A, which was reported as a cathepsin L inhibitor. In our group columbamides were isolated from the marine cyanobacterium Moorena bouillonii. The geometry of the double bond was determined by the coupling constant obtained using non-decoupled heteronuclear single quantum coherence (HSQC). The configuration of chloromethine in a long-chain acyl moiety was determined by the Ohrui method at room temperature using a chiral HPLC column. Columbamide D showed biosurfactant activity. One strain many compounds (OSMAC) is a method to discover new compounds by changing culture conditions. Prior to our experiments, attempts to apply OSMAC in cyanobacteria resulted in the induction or up-regulation of only known compounds. The heat shock culture of the freshwater cyanobacterium Microcystis aeruginosa up-regulated a ribosomal peptide argicyclamide C. At the same time, we discovered bis-prenylated and monoprenylated argicyclamides A and B. More recently iron-limited culture produced hydroxylated argicyclamide A. OSMAC and genome-based screening could lead the discovery of unique biologically active compounds from cyanobacteria.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139088711","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}
Pub Date : 2024-01-01DOI: 10.1248/yakushi.24-00075
Yoshinori Inano, Kayoko Tsuchiya, Ryota Kumano, Go Miura, Hiromitsu Nakasa
Blood purification therapy with cytokine-adsorbing hemofilters has been used to treat sepsis-associated hypercytokinemia. Polymethylmethacrylate (PMMA) hemofilters are frequently used for this purpose; however, adsorption and removal of teicoplanin, a therapeutic agent, have been reported. Similar concerns have been shared regarding daptomycin because its structure resembles that of teicoplanin; nevertheless, there have been no reported effects associated with daptomycin in this context. We studied the adsorption of daptomycin onto a PMMA hemofilter in vitro and investigated its adsorption onto hollow fiber membranes by adding cut PMMA membranes to a daptomycin solution. Additionally, the daptomycin solution was circulated in a dialysis circuit connected to a PMMA hemofilter, and changes in daptomycin content were examined. The daptomycin content decreased immediately after adding the hollow fiber membranes, similar to that observed for teicoplanin. The daptomycin content was lower than that of the standard reagent in the dialysis circuit model, reaching values below the measurement limit after 20 min. These results suggested that daptomycin was adsorbed and removed by the PMMA hemofilter. Encountering this effect during clinical use is plausible; therefore, daptomycin administration via a PMMA hemofilter should be avoided during blood purification therapy.
{"title":"Exploration of Daptomycin Adsorption by Polymethylmethacrylate Hemofilter In Vitro.","authors":"Yoshinori Inano, Kayoko Tsuchiya, Ryota Kumano, Go Miura, Hiromitsu Nakasa","doi":"10.1248/yakushi.24-00075","DOIUrl":"https://doi.org/10.1248/yakushi.24-00075","url":null,"abstract":"<p><p>Blood purification therapy with cytokine-adsorbing hemofilters has been used to treat sepsis-associated hypercytokinemia. Polymethylmethacrylate (PMMA) hemofilters are frequently used for this purpose; however, adsorption and removal of teicoplanin, a therapeutic agent, have been reported. Similar concerns have been shared regarding daptomycin because its structure resembles that of teicoplanin; nevertheless, there have been no reported effects associated with daptomycin in this context. We studied the adsorption of daptomycin onto a PMMA hemofilter in vitro and investigated its adsorption onto hollow fiber membranes by adding cut PMMA membranes to a daptomycin solution. Additionally, the daptomycin solution was circulated in a dialysis circuit connected to a PMMA hemofilter, and changes in daptomycin content were examined. The daptomycin content decreased immediately after adding the hollow fiber membranes, similar to that observed for teicoplanin. The daptomycin content was lower than that of the standard reagent in the dialysis circuit model, reaching values below the measurement limit after 20 min. These results suggested that daptomycin was adsorbed and removed by the PMMA hemofilter. Encountering this effect during clinical use is plausible; therefore, daptomycin administration via a PMMA hemofilter should be avoided during blood purification therapy.</p>","PeriodicalId":23810,"journal":{"name":"Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan","volume":null,"pages":null},"PeriodicalIF":0.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142366744","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}