Journal of Natural Products 最新文献

Comprehensive Cell Biological Investigation of Cytochalasin B Derivatives with Distinct Activities on the Actin Network. 对肌动蛋白网络具有不同活性的细胞分裂素 B 衍生物进行全面的细胞生物学研究。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-11 DOI: 10.1021/acs.jnatprod.4c00676

Mervic D Kagho, Katharina Schmidt, Christopher Lambert, Thomas Kaufmann, Lili Jia, Jan Faix, Klemens Rottner, Marc Stadler, Theresia Stradal, Philipp Klahn

{"title":"Comprehensive Cell Biological Investigation of Cytochalasin B Derivatives with Distinct Activities on the Actin Network.","authors":"Mervic D Kagho, Katharina Schmidt, Christopher Lambert, Thomas Kaufmann, Lili Jia, Jan Faix, Klemens Rottner, Marc Stadler, Theresia Stradal, Philipp Klahn","doi":"10.1021/acs.jnatprod.4c00676","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00676","url":null,"abstract":"In search of a more comprehensive structure-activity relationship (SAR) regarding the inhibitory effect of cytochalasin B (2) on actin polymerization, a virtual docking of 2 onto monomeric actin was conducted. This led to the identification of potentially important functional groups of 2 (i.e., the NH group of the isoindolone core (N-2) and the hydroxy groups at C-7 and C-20) involved in interactions with the residual amino acids of the binding pocket of actin. Chemical modifications of 2 at positions C-7, N-2, and C-20 led to derivatives 3-6, which were analyzed for their bioactivities. Compounds 3-5 exhibited reduced or no cytotoxicity in murine L929 fibroblasts compared to that of 2. Moreover, short- and long-term treatments of human osteosarcoma cells (U-2OS) with 3-6 affected the actin network to a variable extent, partially accompanied by the induction of multinucleation. Derivatives displaying acetylation at C-20 and N-2 were subjected to slow intracellular conversion to highly cytotoxic 2. Together, this study highlights the importance of the hydroxy group at C-7 and the NH function at N-2 for the potency of 2 on the inhibition of actin polymerization.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142398715","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

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 : 2024-10-10 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-10","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

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 : 2024-10-10 DOI: 10.1021/acs.jnatprod.4c00935

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

引用次数: 0

Immunosuppressive Breviane Spiroditerpenoids from Penicillium bialowiezense Isolated from a Medicinal Plant. 从一种药用植物中分离出的青霉 Bialowiezense 中提取的具有免疫抑制作用的 Breviane 疏螺旋体。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-09 DOI: 10.1021/acs.jnatprod.4c00782

Shu-Shuai Chen, Yuan Gao, Li Chen, Xiao Tong, Pei-Qian Wu, Yi Huang, Shi-Jun He, Jian-Min Yue, Bin Zhou

{"title":"Immunosuppressive Breviane Spiroditerpenoids from Penicillium bialowiezense Isolated from a Medicinal Plant.","authors":"Shu-Shuai Chen, Yuan Gao, Li Chen, Xiao Tong, Pei-Qian Wu, Yi Huang, Shi-Jun He, Jian-Min Yue, Bin Zhou","doi":"10.1021/acs.jnatprod.4c00782","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.4c00782","url":null,"abstract":"Breviane spiroditerpenoids are a small group of structurally interesting and complex meroterpenoids. This work focused on an endophytic fungus Penicillium bialowiezense ZBWPQ-27 that was isolated from a medicinal plant Euphorbia neriifolia, leading to the isolation of 15 breviane spiroditerpenoids with four types of polycyclic systems (1-6 and 9-17), and two new carotane sesquiterpenoids (7 and 8). The structures including absolute configurations of the new compounds 1-8 were elucidated by spectroscopic data analysis and electronic circular dichroism (ECD) calculations. In addition, the misassigned NMR data of several resonances of the 5-methyl-TAL motif (E ring) in those of known brevianes (9-15) were corrected by spectroscopic data analysis. Biological tests revealed that brevianes with the type A ring system (6/6/6/5/6) showed moderate to significant immunosuppressive activities, and compound 11 displayed the most potent inhibitory activities against concanavalin A (ConA)-induced T cell proliferation (IC50 4.1 ± 0.2 μM) and lipopolysaccharide (LPS)-induced B cell proliferation (IC50 4.6 ± 0.2 μM), with good SI values of 28 ± 2 and 25 ± 4, respectively.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386401","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

Prorocentin-5: A Cytotoxic Polyketide from the Benthic Marine Dinoflagellate Prorocentrum lima. Prorocentin-5：一种来自底栖海洋双鞭毛藻 Prorocentrum lima 的细胞毒性多酮。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-08 DOI: 10.1021/acs.jnatprod.4c00851

Yunseok Choi, Eun Ju Jeong, Yeong Du Yoo, Jaeyeon Park, Jung-Rae Rho

引用次数: 0

Total Synthesis and Structural Reassignment of the Molt-Inhibiting Marine Alkaloid Erebusinone. 蜕皮抑制性海洋生物碱依瑞布西酮的全合成与结构重定。

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-04 DOI: 10.1021/acs.jnatprod.4c00973

Louisa Tham, Brodie W Bulcock, Samuele Sala, Gareth L Nealon, Gavin R Flematti, Stephen A Moggach, Matthew J Piggott

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 : 2024-10-04 DOI: 10.1021/acs.jnatprod.4c00640

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

引用次数: 0

Maydisens, Sesterterpenoids with Anti-MDR Activity from Bipolaris maydis. Maydisens, Sesterterpenoids with Anti-MDR Activity from Bipolaris maydis.

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2024-10-02 DOI: 10.1021/acs.jnatprod.4c00658

Yong Shen, Nanjin Ding, Lianghu Gu, Mengru Yu, Qin Li, Weiguang Sun, Chunmei Chen, Yonghui Zhang, Hucheng Zhu

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 : 2024-09-30 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","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 : 2024-09-30 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":"https://doi.org/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":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2024-09-30","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