{"title":"Ouhanamide, an Antiparasitic Linear Lipopeptide from a Marine <i>Okeania</i> sp. Cyanobacterium.","authors":"Mizuho Niiyama, Naoaki Kurisawa, Kairi Umeda, Ghulam Jeelani, Adnan Luthfi Agusta, Tomoyoshi Nozaki, Kiyotake Suenaga","doi":"10.1021/acs.jnatprod.5c00281","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00281","url":null,"abstract":"<p><p>Ouhanamide (<b>1</b>), a new linear lipopeptide consisting of a long-chain fatty acid with a β-branched methyl group, was isolated from a marine <i>Okeania</i> sp. cyanobacterium. The overall structure was elucidated by a combination of various spectroscopic analyses, degradation reactions, and derivatizations. Ouhanamide (<b>1</b>) showed selective antiparasitic activity (IC<sub>50</sub> = 1.2 ± 0.1 μM against <i>Trypanosoma brucei rhodesiense</i> and IC<sub>50</sub> = 4.2 ± 0.9 μM against <i>Plasmodium falciparum</i>) without cytotoxicity at 10 μM against HeLa cells.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074930","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}
Franziska Schanbacher, Valerie I C Rebhahn, Markus Schwark, Steffen Breinlinger, Lenka Štenclová, Kristin Röhrborn, Peter Schmieder, Heike Enke, Susan B Wilde, Timo H J Niedermeyer
{"title":"Mining for Halogenated Metabolites of <i>Aetokthonos hydrillicola</i>, the \"Eagle Killer\" Cyanobacterium.","authors":"Franziska Schanbacher, Valerie I C Rebhahn, Markus Schwark, Steffen Breinlinger, Lenka Štenclová, Kristin Röhrborn, Peter Schmieder, Heike Enke, Susan B Wilde, Timo H J Niedermeyer","doi":"10.1021/acs.jnatprod.5c00161","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00161","url":null,"abstract":"<p><p>The cyanobacterium <i>Aetokthonos hydrillicola</i> has recently become famous as the \"eagle killer\", producing the biindole alkaloid aetokthonotoxin (AETX), a pentabrominated neurotoxin causing the wildlife disease vacuolar myelinopathy. HPLC-HRMS<sup>2</sup> analysis of extracts from environmental samples of the cyanobacterium revealed the presence of AETX derivatives and biosynthetic intermediates of the cyanobacterial neurotoxin. Mass spectrometry-based molecular networking and other advanced computational data mining techniques were employed to explore the chemical space of natural AETX derivatives. We identified a total of 43 biosynthetic intermediates and derivatives of AETX, including several iodinated derivatives, a rare halogenation in specialized metabolites of freshwater organisms. Structural characterization of these metabolites showed that most of them are AETX derivatives with varying substitution patterns of the bromo or iodo substituents, but also, AETX biosynthetic intermediates and other biindole derivatives were detected. Cytotoxicity assays of two isolated derivatives and AETX showed that they differ markedly in their activity.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074929","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}
{"title":"Anti-Inflammatory Furylidene Tetronic Acid Derivatives from an Endophytic Fungus <i>Hypoxylon monticulosum</i> ZZ14.","authors":"Yufang Bi, Yuelun Xu, Tianzhi Li, Tao Yuan","doi":"10.1021/acs.jnatprod.5c00291","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00291","url":null,"abstract":"<p><p>Naturally occurring furylidene tetronic acids were rare and structurally unique, typically with a furylidene connected to a furan-2,4-(3<i>H</i>, 5<i>H</i>)dione (tetronic acid moiety). In the current study, seven furylidene tetronic acid derivatives (<b>1</b>-<b>7</b>) were isolated and identified from the endophytic fungus <i>Hypoxylon monticulosum</i> ZZ14, including three new ones, hypoxytetronic acids A and B (<b>1</b> and <b>2</b>) and 2',3'-dihydronodulisporacid A methyl ester (<b>3</b>). Compounds <b>1</b> and <b>2</b> possess an unusual skeleton, with two tetrahydrofurans attached to the tetronic acid moiety. Their absolute configurations were elucidated by custom-DP4+ probability analysis of NMR chemical shifts and ECD calculations. Nodulisporacid A methyl ester (<b>7</b>) significantly inhibited the production of interleukin 6 (IL-6), interleukin 10 (IL-10), nitric oxide (NO), and inducible nitric oxide synthase (iNOS), comparable to the positive control dexamethasone. Several analogues of nodulisporacid A methyl ester were synthesized, and structure-activity relationship studies were performed, suggesting that the conjugated fragment of 1/2/3/1'/2'/3' and the methyl ester group may be the pharmacophores.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074927","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}
Zhi-Ang Chen, Hong-Fei Li, Shan-Shan Huang, Tian Jin, Wen-Zhe Xie, Juan He, Tao Feng
{"title":"Cordycepsterols A-C, Anti-Inflammatory C<sub>30</sub> Ergosterols with a 6/6/6/5/6-Fused Ring System from <i>Cordyceps militaris</i>.","authors":"Zhi-Ang Chen, Hong-Fei Li, Shan-Shan Huang, Tian Jin, Wen-Zhe Xie, Juan He, Tao Feng","doi":"10.1021/acs.jnatprod.5c00452","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00452","url":null,"abstract":"<p><p><i>Cordyceps militaris</i> is a valuable edible and medicinal fungus. Its chemical composition and biological activity have become the focus of attention. In this study, three unusual C<sub>30</sub> ergosterols, cordycepsterols A-C (<b>1</b>-<b>3</b>), have been isolated from this fungus. Their structures have been identified according to extensive spectroscopic methods as well as computational quantum chemistry. They possess an unusual 6/6/6/5/6-fused pentacyclic system which might be derived from a normal ergosterol backbone by adding two skeletal carbons. Compounds <b>1</b>-<b>3</b> exhibit significant inhibitory activity against nitric oxide production with half maximal inhibitory concentration values of 3.0, 0.9, and 2.3 μM, respectively. They could significantly suppress the secretion of tumor necrosis factor-α and interleukin-6 at the concentration of 5 μM, which indicated that <i>C. militaris</i> and its cordycepsterols A-C have a potential anti-inflammatory application prospect.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144074928","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}
{"title":"Discovery of Antibacterial Azaphilone Hybrid Metabolites from Marine-Derived <i>Aspergillus terreus</i> PPS1.","authors":"Yao-Yao Zheng, Xiu Zhang, Ya-Hui Zhang, Meng-Qi Zhang, Zhiqing Liu, Pingyuan Wang, Guang-Shan Yao, Chang-Yun Wang","doi":"10.1021/acs.jnatprod.5c00187","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00187","url":null,"abstract":"<p><p>Three novel azaphilone hybrids (<b>1</b>-<b>3</b>) with two types of structural units, along with four known compounds (<b>4</b>-<b>7</b>), were obtained from the marine sediment-derived fungus <i>Aspergillus terreus</i> PPS1. Asperbenzophilone A (<b>1</b>) features an unprecedented 6/6/6/6 ring system containing a hemiketal group. Butyropyranones I and II (<b>2</b> and <b>3</b>) are equipped with an azaphilone fragment preasperpyranone and a butyrolactone, which are connected through ether bonds. Comprehensive spectroscopic techniques, ECD calculations, and deduction of biosynthetic pathways were used to confirm the planar structures and absolute configurations of the new compounds. Compound <b>2</b> displayed significant anti-MRSA activity. Additionally, compound <b>2</b> exhibited moderate cytotoxic activity on human tumor cell lines 786-O, 5637, MCF-7, A-673, and 293T and medium inhibitory activity against the SARS-CoV-2 main protease (M<sup>pro</sup>/3CL<sup>pro</sup>).</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143951617","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}
Yang Lin, Zheng-Meng Jiang, Xin Liu, Xing-Xing Ji, Ning-Ning Zhang, Zhi-Lu Yu, Shang-Zhen Li, Zi-Yuan Wang, Ze-Bin Weng, Chang-Jiang-Sheng Lai, E-Hu Liu
{"title":"Gut Microbiome-Derived Metabolism Screen System Reveals Dehydrogenation Metabolism of Isorhynchophylline.","authors":"Yang Lin, Zheng-Meng Jiang, Xin Liu, Xing-Xing Ji, Ning-Ning Zhang, Zhi-Lu Yu, Shang-Zhen Li, Zi-Yuan Wang, Ze-Bin Weng, Chang-Jiang-Sheng Lai, E-Hu Liu","doi":"10.1021/acs.jnatprod.5c00069","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00069","url":null,"abstract":"<p><p>Plant-derived natural products are commonly consumed orally and can be structurally modified by the gut microbiota, potentially altering their biological activity. However, high-throughput studies on their microbial metabolism remain limited. This study applied an <i>in vitro</i> screening system for microbiome-derived metabolism using liquid chromatography-mass spectrometry to analyze the metabolism of 200 natural products by human gut microbiota, and successfully annotated 118 natural products metabolized by gut microbiota. For the first time, metabolic reactions of isorhynchophylline and wilforgine in the intestine were documented. Notably, a substantial increase in the plasma concentration of isocorynoxeine was observed in human microbiota-colonized rats following isorhynchophylline administration compared to those without colonization, suggesting that the dehydrogenation of isorhynchophylline by gut microbiota observed in the <i>in vitro</i> screening system also occurs <i>in vivo</i>. 16S rRNA gene sequencing further revealed an increased abundance of <i>Klebsiella</i> and <i>Escherichia-Shigella</i> following isorhynchophylline administration, suggesting that these genera may influence its microbial transformation or pharmacological activity.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953189","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}
Qian Huang, Ni-Ping Li, Song Ang, Wei Huang, Jia-Qing Cao, Ji-Hong Gu, Lei Wang, Zhen-Long Wu, Wen-Cai Ye
{"title":"Dimeric Acylphloroglucinol Derivatives with Anti-MRSA Activities from <i>Chamelaucium uncinatum</i>.","authors":"Qian Huang, Ni-Ping Li, Song Ang, Wei Huang, Jia-Qing Cao, Ji-Hong Gu, Lei Wang, Zhen-Long Wu, Wen-Cai Ye","doi":"10.1021/acs.jnatprod.5c00163","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00163","url":null,"abstract":"<p><p>Chamelauciumols A-I (<b>1</b>-<b>9</b>), nine undescribed dimeric acylphloroglucinol derivatives, were isolated from the aerial parts of <i>Chamelaucium uncinatum</i>. Structurally, compound <b>1</b> featured a new carbon skeleton characterized by an unprecedented prenyl-substituted methanodibenzo[<i>b</i>,<i>f</i>][1,5]dioxocin core. Compounds <b>2</b> and <b>3</b> represented new dimeric scaffolds, consisting of two methylated acylphloroglucinol derivatives linked via prenyl units. Compounds <b>4</b>-<b>9</b> were new phloroglucinol dimers with various linkage patterns. The structures and absolute configurations of these compounds were elucidated by comprehensive spectroscopic data, single-crystal X-ray diffraction analysis, and electronic circular dichroism calculation. Besides, the antibacterial activities against Gram-positive and Gram-negative bacterial strains of the isolates were evaluated. Compounds <b>3</b> and <b>4</b> exhibited potent inhibitory effects against methicillin-resistant <i>Staphylococcus aureus</i> with minimum inhibitory concentration values ranging from 0.5 to 1 μg/mL. A preliminary study on the mechanism of action revealed that compounds <b>3</b> and <b>4</b> exerted anti-MRSA effects through disrupting bacterial cell membrane integrity. Additionally, compounds <b>3</b> and <b>4</b> also demonstrated remarkable antibiofilm activities.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955517","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}
{"title":"Lyciumines A and B: Two Pyrrole-Fused Alkaloids from the Fruits of <i>Lycium barbarum</i>.","authors":"Yan-Jie Zhu, Xiang-Yang Dai, Yi-Lin Zhao, Yu-Guo Ma, Zhen-Zhu Zhao, Cheng-Fu Su, Zhi-You Hao, Dongdong Wang, Hui Chen","doi":"10.1021/acs.jnatprod.5c00385","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00385","url":null,"abstract":"<p><p>Two novel pyrrole-fused alkaloids, lyciumines A (<b>1</b>) and B (<b>2</b>), were isolated from the fruits of <i>Lycium barbarum</i>. Their structures were elucidated by analysis of NMR spectroscopic and MS spectrometric data, along with computational studies. Compound <b>1</b> represents a novel pyrroloindoline alkaloid with a rare 6/5/5/6 tetracyclic system connected with a 2-formyl-5-methylpyrrole moiety via a C-C bond. Compound <b>2</b> features an unusual pyrrole alkaloid with a 5/5/5 tricyclic skeleton. Compound <b>1</b> significantly increases glucose consumption in insulin-resistant HepG2 cells in a dose-dependent manner. Further mechanism investigations demonstrated that compound <b>1</b> regulates glucose metabolism via activating the AMPK/PI3K/Akt signaling pathway.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955064","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}
Won Min Lee, Si-Young Ahn, Gyu Sung Lee, InWha Park, Jonghwan Kim, Seung Hwan Lee, Sullim Lee, Chung Sub Kim
{"title":"Discovery and Biosynthesis of Indole-Functionalized Metabolites from the Human Blood Bacterium, <i>Paracoccus sanguinis</i>, and Their Anti-Skin Aging Activity.","authors":"Won Min Lee, Si-Young Ahn, Gyu Sung Lee, InWha Park, Jonghwan Kim, Seung Hwan Lee, Sullim Lee, Chung Sub Kim","doi":"10.1021/acs.jnatprod.4c01354","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c01354","url":null,"abstract":"<p><p>The human microbiome plays a crucial role in health and disease, with microbial metabolites acting as key mediators of physiological processes. While extensive research has focused on gut-derived microbes, the metabolic contributions of blood-derived bacteria remain underexplored. Here, we investigate the facultative anaerobe <i>Paracoccus sanguinis</i>, a Gram-negative bacterium isolated from human blood, and its metabolome, revealing insights into its potential impacts on health and disease. Using advanced analytical methods, we characterized 12 metabolites (<b>1</b>-<b>12</b>), including six novel compounds (<b>1</b>-<b>3</b>, <b>9</b>, <b>10</b>, and <b>12</b>). Biosynthetic studies demonstrated that these metabolites are derived through enzymatic and nonenzymatic pathways. Functional evaluations revealed significant antiaging activities for <b>1</b>, <b>6</b>, and <b>11</b> in TNF-α-stimulated normal human dermal fibroblasts (NHDFs), including suppression of reactive oxygen species (ROS), inhibition of matrix metalloproteinase-1 (MMP-1) secretion, and reduction of inflammatory cytokines interleukin (IL)-6 and IL-8. Among the tested compounds, <b>11</b> exhibited the highest antiaging efficacy, highlighting its potential as a candidate for therapeutic applications targeting skin aging. This study elucidates the biosynthetic pathways of <i>P. sanguinis</i> metabolites and their antiskin aging activity, underscoring their potential in modulating skin health and offering novel insights into the functional roles of blood-derived microbiota in human health.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955063","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}
{"title":"Asteltoxins I-T: Polyketides from a Plant Endophytic Strain of <i>Pochonia bulbillosa</i>.","authors":"Chun-Lun Qin, Zheng Li, Zi-Jian Huang, Jin-Ling Chang, Junjun Liu, Fang-Fang Duan, Xiaoyi Wei, Han-Li Ruan","doi":"10.1021/acs.jnatprod.5c00303","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00303","url":null,"abstract":"<p><p>Asteltoxins I-T (<b>1</b>-<b>12</b>), 12 asteltoxin-type polyketides, together with four known analogues (<b>13</b>-<b>16</b>), were isolated from an endophytic fungus <i>Pochonia bulbillosa</i> KNI755. Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism (ECD) calculations. Compound <b>1</b> featured a tetrahydro-2<i>H</i>-pyran-linked asteltoxin heterodimer incorporating a clavatol unit. Compounds <b>2</b> and <b>3</b> demonstrated unique tetrahydro-1,4-oxazine-linked asteltoxin heterodimers comprising a diphenyl ether unit. Compounds <b>4</b>-<b>7</b> presented unusual 1,4-dioxane-linked asteltoxin heterodimers also containing a diphenyl ether unit. Compounds <b>1</b>-<b>7</b> were immunosuppressive against concanavalin A (ConA)-induced T cell proliferation and lipopolysaccharide (LPS)-induced B cell proliferation with EC<sub>50</sub> values ranging from 9.2 to 26 μM and from 6.3 to 27 μM, respectively. Compound <b>1</b> exhibited inhibitory activity against the HCT116 human cancer cell line with an IC<sub>50</sub> value of 10 μM.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143955892","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}