Journal of Natural Products 最新文献_第10页

Biologically Active Natural Products: Source and Inspiration for Drug R&D. 生物活性天然产品：药物研发的源泉和灵感。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 DOI: 10.1021/acs.jnatprod.4c01158

Jayanta Haldar, Christa E Müller, Philip J Proteau

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Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane. 笼黄酮莫来酸通过靶向细菌膜对抗耐万古霉素肠球菌感染的活性

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-10-10 DOI: 10.1021/acs.jnatprod.4c00425

Dong-Mei Tang, Zhao-Jie Wang, Wen-Biao Zu, Yue-Ming Jiang, Yan-Yan Zhu, Mei-Zhen Wei, Xiao-Dong Luo

{"title":"Activity of the Caged Xanthone Morellic Acid against Vancomycin-Resistant Enterococcus Infection by Targeting the Bacterial Membrane.","authors":"Dong-Mei Tang, Zhao-Jie Wang, Wen-Biao Zu, Yue-Ming Jiang, Yan-Yan Zhu, Mei-Zhen Wei, Xiao-Dong Luo","doi":"10.1021/acs.jnatprod.4c00425","DOIUrl":"10.1021/acs.jnatprod.4c00425","url":null,"abstract":"Vancomycin-resistant Enterococcus (VRE) is an important nosocomial opportunistic pathogen that is associated with multidrug resistance. Here, we demonstrate that morellic acid inhibits VRE by restoring its sensitivity to vancomycin and ampicillin with low drug resistance and efficient biofilm clearance effects. Morellic acid binds to inner membrane phospholipids, such as phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CL) of VRE, such that the fluidity and proton-motive force (PMF) interfere with the damaged inner membrane, causing intracellular reactive oxygen species (ROS) accumulation and bacterial death. Transcriptional analyses supported this effect on inner membrane-related pathways such as fatty acid biosynthesis and glycerophospholipid metabolism. Moreover, morellic acid significantly eliminated residual bacteria in the spleen, liver, kidneys, and abdominal effusion in mice. Our findings indicate the potential applications of morellic acid as an antibacterial agent or adjuvant for treating VRE infections.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2366-2375"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conformational Sampling in Computational Studies of Natural Products: Why Is It Important? 天然产物计算研究中的构象取样：为何重要？

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-24 DOI: 10.1021/acs.jnatprod.4c00852

Yuchen Zhou, Ingso Limbu, Mary J Garson, Elizabeth H Krenske

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Isolation and Characterization of the Cyanobacterial Macrolide Glycoside Moorenaside, an Anti-Inflammatory Analogue of Aurisides Targeting the Keap1/Nrf2 Pathway. 蓝藻大环内酯糖苷 Moorenaside 的分离与特性分析--一种针对 Keap1/Nrf2 通路的 Aurisides 抗炎类似物

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-24 DOI: 10.1021/acs.jnatprod.4c00420

Fatma H Al-Awadhi, Sofia Kokkaliari, Ranjala Ratnayake, Valerie J Paul, Hendrik Luesch

{"title":"Isolation and Characterization of the Cyanobacterial Macrolide Glycoside Moorenaside, an Anti-Inflammatory Analogue of Aurisides Targeting the Keap1/Nrf2 Pathway.","authors":"Fatma H Al-Awadhi, Sofia Kokkaliari, Ranjala Ratnayake, Valerie J Paul, Hendrik Luesch","doi":"10.1021/acs.jnatprod.4c00420","DOIUrl":"10.1021/acs.jnatprod.4c00420","url":null,"abstract":"A new 14-membered ring brominated macrolide glycoside, named moorenaside (1), was discovered from a marine cyanobacterial sample collected from Shands Key in Florida. The structure of 1 was established by analysis of spectroscopic data including its relative configuration. The absolute configuration was inferred from optical rotation data and comparison with related compounds. The structure of 1 features an α,β-unsaturated carbonyl system, which is also found in aurisides. The presence of this motif in 1 prompted us to evaluate its effect on Keap1/Nrf2 signaling, a cytoprotective pathway culminating in the activation of antioxidant genes activated upstream by the cysteine alkylation of Keap1. Moorenaside exhibited moderate ARE luciferase activity at 32 μM. Due to the established crosstalk between Nrf2 and NF-κB pathways, we investigated the anti-inflammatory effects of 1 in LPS-induced mouse macrophages (RAW264.7 cells), a commonly used model for inflammation. Moorenaside significantly upregulated Nqo1 (Nrf2 target gene) and downregulated iNos (NF-κB target gene) at 32 μM by 5.0- and 2.5-fold, respectively, resulting in a significant reduction of nitric oxide (NO) levels. Furthermore, we performed RNA-sequencing and demonstrated the transcriptional activity of 1 on a global level and identified canonical pathways and upstream regulators involved in inflammation, immune response, and certain oxidative-stress-underlying diseases such as multiple sclerosis and chronic kidney disease.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2355-2365"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519913/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Further Probing the Properties of a Unique Sponge-derived Alkaloid Through the Isolation of a New (-)-(5E)-(8R)-(14Z)-Mycothiazole Analogue. 通过分离一种新的(-)-(5E)-(8R)-(14Z)-霉噻唑类似物，进一步探索一种独特的海绵生物碱的特性。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-30 DOI: 10.1021/acs.jnatprod.4c00691

Joe A Gerke, Sofia F Odron, Juri Kim, Naibedya Dutta, Jacqueline G Clarke, Joseph Media, David A Coppage, Maria Oorloff, Athena Alcala, Gilberto Garcia, Marissa E F Kang, Cy L Gerke, Jacob C Peterson, Joseph D Morris, Ryo Higuchi-Sanabria, Frederick A Valeriote, Phillip Crews, Tyler A Johnson

{"title":"Further Probing the Properties of a Unique Sponge-derived Alkaloid Through the Isolation of a New (-)-(5E)-(8R)-(14Z)-Mycothiazole Analogue.","authors":"Joe A Gerke, Sofia F Odron, Juri Kim, Naibedya Dutta, Jacqueline G Clarke, Joseph Media, David A Coppage, Maria Oorloff, Athena Alcala, Gilberto Garcia, Marissa E F Kang, Cy L Gerke, Jacob C Peterson, Joseph D Morris, Ryo Higuchi-Sanabria, Frederick A Valeriote, Phillip Crews, Tyler A Johnson","doi":"10.1021/acs.jnatprod.4c00691","DOIUrl":"10.1021/acs.jnatprod.4c00691","url":null,"abstract":"Scale-up isolation of (+)-(5Z)-(8S)-(14Z)-mycothiazole (1) from Vanuatu specimens of C. mycofijiensis to semisynthesize (+)-(5Z)-(8S)-8-O-acetyl-(14Z)-mycothiazole (2) revealed a new diastereomer, (-)-(5E)-(8R)-(14Z)-mycothiazole (4). The structure of 4 was determined using HRMS, NMR, and comparing optical rotation to (-)-(5Z)-(8R)-(14Z)-mycothiazole (3) and 2. The maximum tolerated dose of 2 in mice was 0.1 mg/kg. The IC50 of 4 in PANC-1 and HepG2 cancer cell lines was 111.6 and 115.0 nM. Evaluation of 4 in C. elegans showed similar oxygen consumption compared to 1-2, and all compounds significantly increased the lifespan. The Z orientation at Δ5,6 is crucial for picomolar cytotoxicity but not for mitochondrial inhibition.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2523-2529"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11534373/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Machine Learning Accelerates Screening of Osteoclast Differentiation Inhibitors from Natural Products. 机器学习加速从天然产品中筛选破骨细胞分化抑制剂

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-10-04 DOI: 10.1021/acs.jnatprod.4c00640

Yuki Hitora, Mako Hokaguchi, Yusaku Sadahiro, Takumi Higaki, Sachiko Tsukamoto

引用次数: 0

Semisynthetic Ecdysteroid Cinnamate Esters and tert-Butyl Oxime Ether Derivatives with Trypanocidal Activity. 具有杀锥虫活性的半合成蜕皮激素肉桂酸酯和叔丁基肟醚衍生物。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-10-17 DOI: 10.1021/acs.jnatprod.4c00811

Márton B Háznagy, Gábor Girst, Máté Vágvölgyi, Kaushavi Cholke, Sandhya Radha Krishnan, Jürg Gertsch, Attila Hunyadi

{"title":"Semisynthetic Ecdysteroid Cinnamate Esters and tert-Butyl Oxime Ether Derivatives with Trypanocidal Activity.","authors":"Márton B Háznagy, Gábor Girst, Máté Vágvölgyi, Kaushavi Cholke, Sandhya Radha Krishnan, Jürg Gertsch, Attila Hunyadi","doi":"10.1021/acs.jnatprod.4c00811","DOIUrl":"10.1021/acs.jnatprod.4c00811","url":null,"abstract":"The parasite Trypanosoma cruzi is the causative agent of Chagas disease, a neglected tropical disease that affects the lives of millions of indigenous people in Latin America. As medications to treat Chagas disease are limited to the application of benznidazole and nifurtimox, which are not ideal treatments for the chronic stage of the disease, the search for new antichagasic drug candidates is an important need. Ecdysone has previously been shown to interfere with the life cycle of T. cruzi. Here, we report the biological profiling and subsequent semisynthetic structure optimization of 47 ecdysteroids against T. cruzi with the aim of identifying selective trypanocidal ecdysteroids. Two moderately trypanocidal pharmacophores were identified: ecdysteroids containing a 6-tert-butyl oxime ether and a cinnamic ester moiety. These functional groups were combined into the structures of four new semisynthetic ecdysteroids (44-47), among which 44 exerted potent and selective trypanocidal activity (IC50 < 2 μM). Cellular infection assays showed that ecdysteroid 44 potently and efficiently inhibited amastigote replication as determined by trypomastigote release after cellular infection with an IC50 of 2.7 ± 0.1 μM. The compound was similarly potent to benznidazole (IC50 = 3.8 ± 0.7 μM) and more than 5-fold more cytotoxic toward T. cruzi over RAW264.7 host macrophages. Overall, the ecdysteroid cinnamate ester 44 is a novel trypanocidal lead structure that needs to be further characterized in follow-up studies.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2478-2486"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11519910/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142453370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Penicamins A-L, Polyoxygenated Diterpenes from Penicillium camemberti JSB-7212. 青霉素 A-L，来自卡门贝青霉 JSB-7212 的聚氧二萜。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-10-16 DOI: 10.1021/acs.jnatprod.4c00700

Jiao Pei, Jin-Ling Chang, Qian-Xi Ouyang, Xiao-Gang Peng, Xianggao Meng, An Jin, Han-Li Ruan

引用次数: 0

The Molecules Gateway: A Homogeneous, Searchable Database of 150k Annotated Molecules from Actinomycetes 分子网关：包含 15 万个放线菌注释分子的同质可搜索数据库

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 DOI: 10.1021/acs.jnatprod.4c0085710.1021/acs.jnatprod.4c00857

Matteo Simone, Marianna Iorio, Paolo Monciardini, Massimo Santini, Niccolò Cantù, Arianna Tocchetti, Stefania Serina, Cristina Brunati, Thomas Vernay, Andrea Gentile, Mattia Aracne, Marco Cozzi, Justin J. J. van der Hooft, Margherita Sosio, Stefano Donadio and Sonia I. Maffioli*,

{"title":"The Molecules Gateway: A Homogeneous, Searchable Database of 150k Annotated Molecules from Actinomycetes","authors":"Matteo Simone, Marianna Iorio, Paolo Monciardini, Massimo Santini, Niccolò Cantù, Arianna Tocchetti, Stefania Serina, Cristina Brunati, Thomas Vernay, Andrea Gentile, Mattia Aracne, Marco Cozzi, Justin J. J. van der Hooft, Margherita Sosio, Stefano Donadio and Sonia I. Maffioli*, ","doi":"10.1021/acs.jnatprod.4c0085710.1021/acs.jnatprod.4c00857","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00857https://doi.org/10.1021/acs.jnatprod.4c00857","url":null,"abstract":"Natural products are a sustainable resource for drug discovery, but their identification in complex mixtures remains a daunting task. We present an automated pipeline that compares, harmonizes and ranks the annotations of LC-HRMS data by different tools. When applied to 7,400 extracts derived from 6,566 strains belonging to 86 actinomycete genera, it yielded 150,000 molecules after processing over 50 million MS features. The web-based Molecules Gateway provides a highly interactive access to experimental and calculated data for these molecules, along with the metadata related to extracts and producer strains. We show how the Molecules Gateway can be used to rapidly identify known hard to find microbial products, unreported analogs of known families and not yet described metabolites. The Molecules Gateway, which complements available repositories, contains annotated MS data, both acquired and computationally processed under an identical workflow, making it suitable for global analyses which reveal a large and untapped chemical diversity afforded by actinomycetes.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"87 11","pages":"2615–2628 2615–2628"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142691504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Genome-Led Discovery of the Antibacterial Cyclic Lipopeptide Kutzneridine A and Its Silent Biosynthetic Gene Cluster from Kutzneria Species. 通过基因组发现库茨内里藻抗菌环脂肽 Kutzneridine A 及其沉默生物合成基因簇。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-27 DOI: 10.1021/acs.jnatprod.4c00633

Francisco Javier Ortiz-López, Daniel Oves-Costales, Jaime Felipe Guerrero Garzón, Tetiana Gren, Eva Baggesgaard Sterndorff, Xinglin Jiang, Tue Sparholt Jo Rgensen, Kai Blin, Ignacio Fernández-Pastor, José R Tormo, Jesús Martín, Pilar Sánchez, Mercedes de la Cruz Moreno, Fernando Reyes, Olga Genilloud, Tilmann Weber

{"title":"Genome-Led Discovery of the Antibacterial Cyclic Lipopeptide Kutzneridine A and Its Silent Biosynthetic Gene Cluster from Kutzneria Species.","authors":"Francisco Javier Ortiz-López, Daniel Oves-Costales, Jaime Felipe Guerrero Garzón, Tetiana Gren, Eva Baggesgaard Sterndorff, Xinglin Jiang, Tue Sparholt Jo Rgensen, Kai Blin, Ignacio Fernández-Pastor, José R Tormo, Jesús Martín, Pilar Sánchez, Mercedes de la Cruz Moreno, Fernando Reyes, Olga Genilloud, Tilmann Weber","doi":"10.1021/acs.jnatprod.4c00633","DOIUrl":"10.1021/acs.jnatprod.4c00633","url":null,"abstract":"Genome analysis of Kutzneria sp. CA-103260 revealed a putative lipopeptide-encoding biosynthetic gene cluster (BGC) that was cloned into a bacterial artificial chromosome (BAC) and heterologously expressed in Streptomyces coelicolor M1152. As a result, a novel cyclic lipo-tetrapeptide containing two diaminopropionic acid residues and an exotic N,N-acetonide ring, kutzneridine A (1), was isolated and structurally characterized. Evaluation of the extraction conditions and isotope-labeling chemical modifications showed that the acetonide ring originated from acetone during isolation. The BGC was analyzed in silico and a biosynthetic pathway to 1 was proposed. Kutzneridine A displayed remarkable antibacterial activity against methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococci.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2515-2522"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0