Journal of Natural Products 最新文献

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Host–Pathogen Interaction Activated Biosynthesis of Natural Products 宿主-病原体相互作用激活天然产物的生物合成。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-28 DOI: 10.1021/acs.jnatprod.5c00776
Yukiko Ujie, , , Shun Saito, , , Chisato Iwata, , , Ruri Kuwahara, , , Shinji Kishimoto, , , Kenji Watanabe, , , Yoshikuni Goto, , , Kenji Ogawa, , , Yasumasa Hara, , , Yoko Kusuya, , , Hiroki Takahashi, , , Takashi Yaguchi, , , Masami Ishibashi, , and , Midori A. Arai*, 
{"title":"Host–Pathogen Interaction Activated Biosynthesis of Natural Products","authors":"Yukiko Ujie,&nbsp;, ,&nbsp;Shun Saito,&nbsp;, ,&nbsp;Chisato Iwata,&nbsp;, ,&nbsp;Ruri Kuwahara,&nbsp;, ,&nbsp;Shinji Kishimoto,&nbsp;, ,&nbsp;Kenji Watanabe,&nbsp;, ,&nbsp;Yoshikuni Goto,&nbsp;, ,&nbsp;Kenji Ogawa,&nbsp;, ,&nbsp;Yasumasa Hara,&nbsp;, ,&nbsp;Yoko Kusuya,&nbsp;, ,&nbsp;Hiroki Takahashi,&nbsp;, ,&nbsp;Takashi Yaguchi,&nbsp;, ,&nbsp;Masami Ishibashi,&nbsp;, and ,&nbsp;Midori A. Arai*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00776","DOIUrl":"10.1021/acs.jnatprod.5c00776","url":null,"abstract":"<p >The way immune cells attack pathogenic microorganisms might trigger pathogens to produce compounds that promote their survival. Based on this idea, we constructed a coculture system of pathogenic fungi and immune cells and isolated fumigatinolactone (<b>1</b>) as a new natural product by coculture of <i>Aspergillus fumigatus</i> IFM 60237 with RAW264 mouse macrophage-like cells. Fumigatinolactone (<b>1</b>) was produced via a nonenzymatic coupling reaction between fumigatin (<b>4</b>) and a new type of intermediate fumarylazlactone (<b>5</b>). An investigation of the interaction mechanism between the fungi and cells revealed that the survival interaction between pathogen and immune cells played key roles. Surprisingly, fungi showed a response to nitric oxide (NO), which was produced by macrophages, resulting in the production of <b>4</b>. In addition, an iron starvation condition triggered the production of <b>5</b>. Finally, <b>1</b> was obtained by these two mechanisms. Furthermore, compounds <b>1</b>–<b>4</b>, particularly <b>4</b>, showed inhibition of NO production from RAW264, which might be a defense action for macrophage by fungi. This is the first example of elucidation of interaction mechanisms between pathogen and immune cells for activation of silent genes to produce a new compound. These findings suggest that host–pathogen survival interaction may increase the production of secondary metabolites from fungi.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2204–2215"},"PeriodicalIF":3.6,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936135","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
Identification and Stereoselective Total Synthesis of an Insect Homosesquiterpene from the Clonal Raider Ant Ooceraea biroi 克隆蚁卵母蚁同源半萜的鉴定及立体选择性合成。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-27 DOI: 10.1021/acs.jnatprod.5c00656
Ryan M. Alam*, , , Yoko Nakamura, , , Stefan Bartram, , , Nico Ueberschaar, , , Tim Zetzsche, , , Yuko Ulrich, , , Sarah E. O’Connor*, , and , Tobias G. Köllner*, 
{"title":"Identification and Stereoselective Total Synthesis of an Insect Homosesquiterpene from the Clonal Raider Ant Ooceraea biroi","authors":"Ryan M. Alam*,&nbsp;, ,&nbsp;Yoko Nakamura,&nbsp;, ,&nbsp;Stefan Bartram,&nbsp;, ,&nbsp;Nico Ueberschaar,&nbsp;, ,&nbsp;Tim Zetzsche,&nbsp;, ,&nbsp;Yuko Ulrich,&nbsp;, ,&nbsp;Sarah E. O’Connor*,&nbsp;, and ,&nbsp;Tobias G. Köllner*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00656","DOIUrl":"10.1021/acs.jnatprod.5c00656","url":null,"abstract":"<p >Ants typically demonstrate a high level of complex social behavior that is largely mediated by chemical communication. In recent years, the Clonal raider ant <i>Ooceraea biroi</i> has become a promising model system for the study of social behavior in ants. Here we report the profile of extracted volatiles from <i>O</i>. <i>biroi</i> and, following detection of an α-homofarnesene as the major component, unambiguously confirm its structural identity as (3<i>Z</i>,6<i>E</i>)-14-methyl-α-farnesene through preparative stereoselective total synthesis.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2107–2116"},"PeriodicalIF":3.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.5c00656","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936178","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
Asymmetric Total Synthesis of (+)-Karanone: An Important Aroma Compound in Fine Agarwood 沉香中一种重要芳香化合物(+)-卡拉酮的不对称全合成。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-26 DOI: 10.1021/acs.jnatprod.5c00838
Yuta Inori, , , Hirosato Takikawa, , and , Yusuke Ogura*, 
{"title":"Asymmetric Total Synthesis of (+)-Karanone: An Important Aroma Compound in Fine Agarwood","authors":"Yuta Inori,&nbsp;, ,&nbsp;Hirosato Takikawa,&nbsp;, and ,&nbsp;Yusuke Ogura*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00838","DOIUrl":"10.1021/acs.jnatprod.5c00838","url":null,"abstract":"<p >The first asymmetric total synthesis of (+)-karanone, a key aroma compound in high-grade agarwood (“Kyara”), was accomplished in 17 steps from 4-penten-2-ol. The key stereocenters at C7, C4, and C5 were introduced via asymmetric aldol condensation and Ireland–Claisen rearrangement. The oxygen-functional group at C8 was formed through oxidative rearrangement, and the bicyclic core of (+)-karanone was constructed by ring-closing metathesis. Two related compounds, namely (+)-4-<i>epi</i>-karanone and (+)-warburgiadione, were also synthesized. Studies of the structure–odor relationship among (+)-karanone, (+)-4-<i>epi</i>-karanone, and (+)-warburgiadione were also performed.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2216–2224"},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936157","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
Structure Determination and Biosynthesis of Dapalides A–C, Glycosylated Kahalalide F Analogues from the Marine Cyanobacterium Dapis sp 海洋蓝藻中糖基化卡halalide F类似物的结构测定和生物合成
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-26 DOI: 10.1021/acs.jnatprod.5c00757
Emma K. Ellis, , , Laura P. Ióca, , , Jie Liu, , , Manyun Chen, , , Steven D. Bruner, , , Yousong Ding, , , Valerie J. Paul, , , Mohamed S. Donia*, , and , Hendrik Luesch*, 
{"title":"Structure Determination and Biosynthesis of Dapalides A–C, Glycosylated Kahalalide F Analogues from the Marine Cyanobacterium Dapis sp","authors":"Emma K. Ellis,&nbsp;, ,&nbsp;Laura P. Ióca,&nbsp;, ,&nbsp;Jie Liu,&nbsp;, ,&nbsp;Manyun Chen,&nbsp;, ,&nbsp;Steven D. Bruner,&nbsp;, ,&nbsp;Yousong Ding,&nbsp;, ,&nbsp;Valerie J. Paul,&nbsp;, ,&nbsp;Mohamed S. Donia*,&nbsp;, and ,&nbsp;Hendrik Luesch*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00757","DOIUrl":"10.1021/acs.jnatprod.5c00757","url":null,"abstract":"<p >Kahalalides were originally isolated from the marine mollusk <i>Elysia rufescens</i> and its green algal diet <i>Bryopsis</i> sp., but the true producer was revealed as the obligate bacterial symbiont <i>Candidatus</i> Endobryopsis kahalalidefaciens, residing within <i>Bryopsis</i> sp. The most notable is kahalalide F, a broad-spectrum antitumor depsipeptide that entered the clinic but failed from lack of efficacy. We have isolated three new glycosylated analogues of kahalalide F, termed dapalides A–C (<b>1</b>–<b>3</b>), from a marine cyanobacterium, <i>Dapis</i> sp., collected from Guam. The planar structures were determined by extensive NMR coupled with mass spectrometry. Acid hydrolysis of <b>1</b> using amino acid analysis revealed the absolute configuration of singlet and a mixture of duplicate amino acids. Metagenomic analysis unveiled a biosynthetic gene cluster (BGC) with a nonribosomal peptide synthetase (NRPS) system and downstream glycosylation enzymes, which assisted the configurational assignment through epimerization domain analysis. The discovered BGC, termed <i>dap</i>, was assigned to a high-quality metagenome-assembled genome of the <i>Dapis</i> sp. Dapalide A (<b>1</b>) was subjected to phenotypic bioassays and exhibited weak anticancer cytotoxicity. This discovery expands the chemical diversity of the kahalalide F family, suggests their broad ecological role across diverse organisms, and presents an intriguing case of natural product biosynthesis evolution.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2138–2150"},"PeriodicalIF":3.6,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.5c00757","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145051420","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
Identification of Cembrane Diterpenoids from Sinularia sp. That Reduce the Viability of Diffuse Pleural Mesothelioma Cell Lines 降低弥漫性胸膜间皮瘤细胞株活力的膜二萜类化合物的鉴定。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-25 DOI: 10.1021/acs.jnatprod.5c00786
Maria Orfanoudaki, , , Anam F. Shaikh, , , Dongdong Wang, , , Vivek Singh, , , Lin Du, , , Jennifer A. Wilson, , , Antony Wamiru, , , Ekaterina I. Goncharova, , , Nathanael Pruett, , , Chuong D. Hoang*, , , Brice A. P. Wilson*, , and , Barry R. O’Keefe*, 
{"title":"Identification of Cembrane Diterpenoids from Sinularia sp. That Reduce the Viability of Diffuse Pleural Mesothelioma Cell Lines","authors":"Maria Orfanoudaki,&nbsp;, ,&nbsp;Anam F. Shaikh,&nbsp;, ,&nbsp;Dongdong Wang,&nbsp;, ,&nbsp;Vivek Singh,&nbsp;, ,&nbsp;Lin Du,&nbsp;, ,&nbsp;Jennifer A. Wilson,&nbsp;, ,&nbsp;Antony Wamiru,&nbsp;, ,&nbsp;Ekaterina I. Goncharova,&nbsp;, ,&nbsp;Nathanael Pruett,&nbsp;, ,&nbsp;Chuong D. Hoang*,&nbsp;, ,&nbsp;Brice A. P. Wilson*,&nbsp;, and ,&nbsp;Barry R. O’Keefe*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00786","DOIUrl":"10.1021/acs.jnatprod.5c00786","url":null,"abstract":"<p >Diffuse pleural mesothelioma (DPM) is a rare but aggressive late-onset cancer. A high-throughput screen of a natural product fraction library identified fractions derived from an aqueous extract of <i>Sinularia</i> sp. soft coral that reduced the viability of DPM cell lines. Bioassay-guided fractionation of the parent extract resulted in the identification of 13 cembrane diterpenoids, including nine new natural products sinulariolones B–J (<b>1</b>–<b>4</b>, and <b>7</b>–<b>11</b>), as the active principles. The planar structures of the new compounds were established by the analysis of NMR spectroscopic and MS spectrometric data. Their relative and absolute configurations were determined using a combined approach, including NOESY interpretation, modified Mosher’s method, ECD simulation, and single-crystal X-ray diffraction. All pure metabolites were tested for their effects on the viability of the DPM cell lines, and compounds <b>2</b>, <b>3</b>, <b>8</b>, and <b>9</b> demonstrated low micromolar potency against these cancer cell lines.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2193–2203"},"PeriodicalIF":3.6,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.5c00786","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936102","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
Construction of a New Drug and Agrochemical Candidates Screening Platform Utilizing Drug-Hypersensitive Fission Yeast to Discover Overlooked Natural Products 利用药物超敏裂变酵母发现被忽视的天然产物构建新的药物和农化候选物筛选平台。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-23 DOI: 10.1021/acs.jnatprod.5c00598
Aoi Kimishima, , , Sota Negami, , , Sota Honma, , , Shigehiro A. Kawashima, , , Yoko Yashiroda, , , Shin-ichi Fuji, , , Hiroki Kojima, , , Toshiyuki Tokiwa, , , Akihiro Sugawara, , , Yukiko Ujie, , , Akio Abe, , , Takumi Chinen, , , Minoru Yoshida, , , Takeo Usui, , and , Yukihiro Asami*, 
{"title":"Construction of a New Drug and Agrochemical Candidates Screening Platform Utilizing Drug-Hypersensitive Fission Yeast to Discover Overlooked Natural Products","authors":"Aoi Kimishima,&nbsp;, ,&nbsp;Sota Negami,&nbsp;, ,&nbsp;Sota Honma,&nbsp;, ,&nbsp;Shigehiro A. Kawashima,&nbsp;, ,&nbsp;Yoko Yashiroda,&nbsp;, ,&nbsp;Shin-ichi Fuji,&nbsp;, ,&nbsp;Hiroki Kojima,&nbsp;, ,&nbsp;Toshiyuki Tokiwa,&nbsp;, ,&nbsp;Akihiro Sugawara,&nbsp;, ,&nbsp;Yukiko Ujie,&nbsp;, ,&nbsp;Akio Abe,&nbsp;, ,&nbsp;Takumi Chinen,&nbsp;, ,&nbsp;Minoru Yoshida,&nbsp;, ,&nbsp;Takeo Usui,&nbsp;, and ,&nbsp;Yukihiro Asami*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00598","DOIUrl":"10.1021/acs.jnatprod.5c00598","url":null,"abstract":"<p >Natural products exhibiting selective or preferential antifungal activity against fission yeast over budding yeast might contribute greatly to new discoveries in the life sciences and new drug and agrochemical development. However, it is difficult to discover new drug and agrochemical candidates in the fission yeast screening system due to its low drug sensitivity. In this study, we constructed a new antifungal drug and agrochemical candidate screening platform using a drug-hypersensitive fission yeast strain. We executed antifungal activity profiling of our natural compound and microbial libraries against drug-hypersensitive fission yeast and multidrug-sensitive budding yeast. Ultimately, we identified MS-347a as a promising agrochemical candidate due to its excellent activity against the rice blast fungus.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2090–2096"},"PeriodicalIF":3.6,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936180","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
Glycinocins E–H, Antimicrobial Lipopeptides Produced by a Streptomyces Strain 链霉菌菌株产生的抗菌脂肽甘氨酸E-H。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-22 DOI: 10.1021/acs.jnatprod.5c00740
Ignacio Fernández-Pastor*, , , Victor González-Menéndez, , , Ignacio González, , , Pilar Sanchez, , , Rachel Serrano, , , Thomas A Mackenzie, , , Daniel Oves-Costales, , , Manuel Casares Porcel, , , Olga Genilloud, , and , Fernando Reyes*, 
{"title":"Glycinocins E–H, Antimicrobial Lipopeptides Produced by a Streptomyces Strain","authors":"Ignacio Fernández-Pastor*,&nbsp;, ,&nbsp;Victor González-Menéndez,&nbsp;, ,&nbsp;Ignacio González,&nbsp;, ,&nbsp;Pilar Sanchez,&nbsp;, ,&nbsp;Rachel Serrano,&nbsp;, ,&nbsp;Thomas A Mackenzie,&nbsp;, ,&nbsp;Daniel Oves-Costales,&nbsp;, ,&nbsp;Manuel Casares Porcel,&nbsp;, ,&nbsp;Olga Genilloud,&nbsp;, and ,&nbsp;Fernando Reyes*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00740","DOIUrl":"10.1021/acs.jnatprod.5c00740","url":null,"abstract":"<p >In an antifungal screening of extracts from microbial strains isolated from gypsum outcrops in Granada, Spain, four new cyclic lipopeptides, glycinocins E–H (<b>1</b>–<b>4</b>), were identified from <i>Streptomyces</i> sp. CA-297274 and exhibited potent activity against <i>Zymoseptoria tritici</i>, the causal agent of septoria tritici blotch of wheat. Isolation and structure elucidation performed using HR-MS/MS, 1D and 2D NMR, and Marfey’s analyses, revealed that structures contained an Asp-Gly-Asp-Gly motif in the peptide scaffold, typical of calcium-dependent antibiotics. Genome sequencing and bioinformatic analysis of the strain uncovered a biosynthetic gene cluster consistent with the production of these compounds and helped to correct the absolute configuration determined by Marfey’s analysis of some amino acid residues. The isolated metabolites displayed notable antifungal activity against <i>Z. tritici</i>, with minimum inhibitory concentration values in the micromolar range (Compound <b>4</b>, 9.5 μM), and calcium-dependent antibacterial activity against methicillin-resistant <i>Staphylococcus aureus</i> (5.2 μM for <b>4</b>) and vancomycin-resistant <i>Enterococcus faecium</i> (3.0 μM for <b>4</b>), as anticipated by their structural analysis. Glycinocins E–H displayed no cytotoxicity against the human liver cancer cell line HepG2. These findings expand the chemical diversity of calcium-dependent antibiotics and highlight the ecological and therapeutic potential of extremophile-derived actinomycetes as a source of novel bioactive compounds.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2127–2137"},"PeriodicalIF":3.6,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936087","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
Effective Membrane Permeabilization of Methicillin-Resistant Staphylococcus aureus by Prenylated Phenolics 戊酰化苯酚对耐甲氧西林金黄色葡萄球菌的有效膜渗透作用。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-19 DOI: 10.1021/acs.jnatprod.5c00540
Janniek H. Ritsema, , , Nynke I. Kramer, , , Wouter J. C. de Bruijn, , , Sarah van Dinteren, , , Maurice C. R. Franssen, , , Jean-Paul Vincken, , and , Carla Araya-Cloutier*, 
{"title":"Effective Membrane Permeabilization of Methicillin-Resistant Staphylococcus aureus by Prenylated Phenolics","authors":"Janniek H. Ritsema,&nbsp;, ,&nbsp;Nynke I. Kramer,&nbsp;, ,&nbsp;Wouter J. C. de Bruijn,&nbsp;, ,&nbsp;Sarah van Dinteren,&nbsp;, ,&nbsp;Maurice C. R. Franssen,&nbsp;, ,&nbsp;Jean-Paul Vincken,&nbsp;, and ,&nbsp;Carla Araya-Cloutier*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00540","DOIUrl":"10.1021/acs.jnatprod.5c00540","url":null,"abstract":"<p >Prenylated phenolics are plant-derived compounds with antimicrobial activity against methicillin-resistant <i>Staphylococcus aureus</i> (MRSA), acting by targeting membranes resulting in fast permeabilization. Studies quantifying their membrane permeabilization capacity are lacking, limiting our understanding of the structural properties driving this effect. This study evaluated antimicrobial activity and permeabilization efficacy of 36 C- and O-prenylated phenolics, including 11 C- and O-prenylated phenolics chemically synthesized for this study. Minimum inhibitory concentrations (MICs) were obtained using the broth microdilution assay. Membrane permeabilization was measured by propidium iodide uptake using fluorescence spectrometry and microscopy. The most potent MRSA permeabilizers were luteone (<b>29</b>) and neobavaisoflavone (<b>22</b>), with EC<sub>10</sub> of 27 ± 7 and 28 ± 8 μg mL<sup>–1</sup>, respectively. Diprenylated phenolics showed a strong negative correlation between permeabilization and their hydrophobic-to-polar surface area ratio (<i>r</i><sub>pearson</sub> = 0.88). For monoprenylated phenolics, prenyl configuration (chain) and molecular shape (globular) were important for effective permeabilization. Interestingly, potency of antimicrobial prenylated phenolics (MIC ≤ 50 μg mL<sup>–1</sup>) was not correlated to permeabilization potency, suggesting other mechanisms of action in addition to membrane permeabilization. These quantitative findings on membrane permeabilization by prenylated phenolics contribute to our mechanistic understanding of how these compounds can inhibit microbial growth.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2065–2075"},"PeriodicalIF":3.6,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.5c00540","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870303","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
Unraveling the Intricate Roles of Plant Secondary Metabolites in Mitigating Bacterial Multidrug Resistance: Challenges and Prospects 揭示植物次生代谢物在减轻细菌多药耐药中的复杂作用:挑战与展望。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-18 DOI: 10.1021/acs.jnatprod.5c00349
Uttam, , , Ranjeet Kumar, , , Anchal Singh*, , and , Deepika Biswas*, 
{"title":"Unraveling the Intricate Roles of Plant Secondary Metabolites in Mitigating Bacterial Multidrug Resistance: Challenges and Prospects","authors":"Uttam,&nbsp;, ,&nbsp;Ranjeet Kumar,&nbsp;, ,&nbsp;Anchal Singh*,&nbsp;, and ,&nbsp;Deepika Biswas*,&nbsp;","doi":"10.1021/acs.jnatprod.5c00349","DOIUrl":"10.1021/acs.jnatprod.5c00349","url":null,"abstract":"<p >Secondary metabolites are natural compounds produced by medicinal plants and have long served a crucial role in the prevention and treatment of microbial infections, showcasing their potential over conventional antimicrobial therapies. They have emerged as vital components in agronomy, pharmacy, and international markets due to their growing demand as raw materials for pharmaceutical applications and their increasing utility in daily life. These natural products offer a promising alternative to traditional antibiotics, particularly in combating antibiotic resistance and controlling bacterial infections through novel mechanisms. Secondary metabolites of medicinal plants can disrupt the various resistance mechanisms in bacteria, like the quorum sensing system of bacteria, and also interfere with the cellular mechanism of bacteria, <i>e.g.</i>, inhibition of signal molecule production, degradation of signal molecules, blocking signal receptors, disruption of signal transduction, modulation of gene expression, inhibition of synthesis of DNA and proteins, blocking of oxidative respiration, etc. This present Review elucidates the <i>in vitro</i> antibacterial efficacy and mechanisms of various secondary metabolites, such as alkaloids, flavonoids, tannins, and terpenoids, extracted from medicinal plants. Also, the study highlights the importance of bioactive compounds for managing drug resistance in highly pathogenic bacterial infections and other pharmaceutical applications.</p>","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 9","pages":"2247–2258"},"PeriodicalIF":3.6,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144870304","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
Quinine and Quinidine Derivatives as Photosensitizers for Photodynamic Inactivation of Bacterial Pathogens 奎宁及其衍生物在细菌性致病菌光动力失活中的光敏剂作用。
IF 3.6 2区 生物学
Journal of Natural Products Pub Date : 2025-08-12 DOI: 10.1021/acs.jnatprod.5c00570
Irena Maliszewska*, Anna Zdubek, Błażej Dziuk and Przemysław Boratyński, 
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