Journal of Natural Products 最新文献_第8页

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

Semisynthetic Studies Establish a Role for Conjugate Halide Exchange in the Formation of Chlorinated Pyrroloiminoquinones and Related Alkaloids. 半合成研究确定了共轭卤化物交换在形成氯化吡咯并喹酮和相关生物碱中的作用。

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.4c00549

Samuele Sala, Masashi Shimomura, Louisa Tham, Juri Sakata, Alexandre N Sobolev, Stephen A Moggach, Jane Fromont, Oliver Gomez, Matthew J Piggott, Hidetoshi Tokuyama, Scott G Stewart, Gavin R Flematti

{"title":"Semisynthetic Studies Establish a Role for Conjugate Halide Exchange in the Formation of Chlorinated Pyrroloiminoquinones and Related Alkaloids.","authors":"Samuele Sala, Masashi Shimomura, Louisa Tham, Juri Sakata, Alexandre N Sobolev, Stephen A Moggach, Jane Fromont, Oliver Gomez, Matthew J Piggott, Hidetoshi Tokuyama, Scott G Stewart, Gavin R Flematti","doi":"10.1021/acs.jnatprod.4c00549","DOIUrl":"10.1021/acs.jnatprod.4c00549","url":null,"abstract":"Two novel pyrroloiminoquinone alkaloids, 6-chlorodamirone A and 6-bromodamirone A, have been identified for the first time from the marine sponge Latrunculia sp. (order: Poecilosclerida: family Latrunculiidae), sourced from Western Australia. Alongside these new compounds, seven previously known metabolites were also isolated. Despite being obtained in submilligram quantities, the structures of these natural products were successfully elucidated using high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. To confirm the structures of these newly discovered alkaloids, a semisynthetic approach was employed starting from the more abundant metabolite, damirone A, additionally, single crystal X-ray crystallography was used to validate our structural proposals. The semisynthetic studies suggest that the chlorinated alkaloids are likely formed through a nonenzymatic conjugate halide substitution reaction rather than an enzymatic process. This reactivity parallels that observed in related metabolites, such as the caulibugulones B and C. Furthermore, a biomimetic cascade reaction was attempted to synthesize the spirodienone moiety characteristic of the discorhabdin alkaloids, inspired by the nucleophilic substitution observed in the tricyclic damirone A system. Albeit unsuccessful, these findings provide valuable insight into the reactivity of halogenated pyrroloiminoquinones under various conditions.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2507-2514"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337359","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

Computationally-Assisted Discovery and Assignment of a New Class of 6/6/5/5 Fused-Ring Diterpene Acting as Pregnane X Receptor Ligands from Isodon serra. 通过计算辅助从 Isodon serra 中发现并鉴定一类可作为孕烷 X 受体配体的新型 6/6/5/5 Fused-Ring Diterpene。

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.4c00759

Zhiwei Bian, Xiaoying Liu, Shian Hu, Hongyi Li, Jared S Wood, R Thomas Williamson, Jiabao Liu, Ying Chen, Jin Shi, Carolyn L Cummins, Daneel Ferreira, Yeun-Mun Choo, Shengpeng Wang, Mark T Hamann, Xiaojuan Wang

{"title":"Computationally-Assisted Discovery and Assignment of a New Class of 6/6/5/5 Fused-Ring Diterpene Acting as Pregnane X Receptor Ligands from Isodon serra.","authors":"Zhiwei Bian, Xiaoying Liu, Shian Hu, Hongyi Li, Jared S Wood, R Thomas Williamson, Jiabao Liu, Ying Chen, Jin Shi, Carolyn L Cummins, Daneel Ferreira, Yeun-Mun Choo, Shengpeng Wang, Mark T Hamann, Xiaojuan Wang","doi":"10.1021/acs.jnatprod.4c00759","DOIUrl":"10.1021/acs.jnatprod.4c00759","url":null,"abstract":"We report here the orchestration of molecular ion networking (MoIN) and a set of computationally assisted structural elucidation approaches in the discovery and assignment of a new class of rearranged 4,5-seco-abietane diterpenoids including serra A (1), which possesses an unusual 6/6/5/5 fused-ring skeleton system, together with two previously unreported diterpenoids serras B-C (2-3) and five known compounds were isolated from Isodon serra (I. serra). The structures were elucidated by spectroscopic analysis in conjunction with computationally assisted structure elucidation tools. In silico, serras A-C (1-3) bind well to PXR, suggesting their potential role in reducing inflammation. The results of serra A (1) with hPXR demonstrated agonist activity with an EC50 value of 15 μM. Serra A (1), graciliflorin F (4), gerardianin C (5), 11,12,15-trihydroxy-8,11,13-abietatrien-7-one (6), rabdosin D (7), and 15-hydroxysalprionin (8) exhibited promising anti-inflammatory activities in lipopolysaccharide (LPS)-induced RAW 267.4 cells, and their inhibition rates on NO production were more than 65% at 10 μM.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2459-2467"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306583","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

Looking for Actives in the Haystack: Merging HRMS²-Based Molecular Networking, Chemometrics, and ¹³C NMR-Based Dereplication Approaches. 在干草堆中寻找活性物质：合并基于 HRMS2 的分子网络、化学计量学和基于 13C NMR 的去复制方法。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-28 DOI: 10.1021/acs.jnatprod.4c00647

Manon Meunier, Dimitri Bréard, Séverine Boisard, Patricia Blanchard, Marc Litaudon, Khalijah Awang, Andreas Schinkovitz, Séverine Derbré

{"title":"Looking for Actives in the Haystack: Merging HRMS2-Based Molecular Networking, Chemometrics, and 13C NMR-Based Dereplication Approaches.","authors":"Manon Meunier, Dimitri Bréard, Séverine Boisard, Patricia Blanchard, Marc Litaudon, Khalijah Awang, Andreas Schinkovitz, Séverine Derbré","doi":"10.1021/acs.jnatprod.4c00647","DOIUrl":"10.1021/acs.jnatprod.4c00647","url":null,"abstract":"The identification of bioactive natural products (NPs) in complex mixtures has become an important subject of contemporary NP research. In an attempt to address this challenge, the present work proposes an integrated strategy that combines tandem mass spectrometry (MS2)-based molecular networking (MN), a partial least-squares (PLS) chemometric model, as well as 13C NMR-based dereplication using MixONat software. In addition, an advanced glycation end product (AGEs) assay was used for activity evaluation. The approach was implemented on a Garcinia parvifolia bark extract that comprised a high content of prenylated xanthones and had previously shown a notable inhibitory effect on AGE formation. As a main result, the proposed strategy permitted the identification of potentially active metabolites within complex mixtures and their annotation with a higher level of confidence by NMR data. Overall, this comprehensive approach provides a powerful and efficient solution for the targeting and annotating of active compounds in complex NP mixtures.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":"2398-2407"},"PeriodicalIF":3.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142337357","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

Triantaspirols A-C and Paraphaeolactone Cs from Paraphaeosphaeria sp. KT4192: Sensitivity of CP3 in Distinguishing Close NMR Signals. 来自 Paraphaeosphaeria sp. KT4192 的 Triantaspirols A-C 和 Paraphaeolactone Cs：CP3 在区分近似 NMR 信号方面的灵敏度。

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.4c00935

Ryuhi Kanehara, Yuki Oinuma, Hayato Maeda, Kazuaki Tanaka, Masaru Hashimoto

引用次数: 0

Albusamides A-G: Hydroxylated Fatty Amine Derivatives from the Deep-Sea-Derived Actinomycete Streptomyces albus 228DD-066 and Their Cytotoxic Activity. Albusamides A-G：深海放线菌 Streptomyces albus 228DD-066 的羟化脂肪胺衍生物及其细胞毒活性。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-25 Epub Date: 2024-09-21 DOI: 10.1021/acs.jnatprod.4c00683

Hee Jae Shin, Su-Yeon Jung, Jong Soon Kang, Chang-Su Heo, Sun Joo Park

引用次数: 0

Maduraflavacins A-E, Unusual Phenyl Polyene Metabolites Produced by a Rare Marine-Derived Actinomadura sp. 一种罕见的海洋衍生放线菌产生的非同寻常的苯基多烯代谢物 Maduraflavacins A-E

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.4c00836

Yan Zou, Jing Shi, Jia Lin Sun, Ling Yu Li, Zhang Yuan Yan, Zhi Kai Guo, Rui Hua Jiao

引用次数: 0