Journal of Natural Products 最新文献_第6页

Dereplication of Sesquiterpene-Proline Conjugates and Phenalenones from Penicillium sp. CNUFC-EML-48 Using Molecular Networking and Cytotoxicity Profiling 利用分子网络和细胞毒性分析从青霉属cnfc - eml -48中分离倍半萜-脯氨酸偶联物和苯烯酮。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-28 DOI: 10.1021/acs.jnatprod.5c00630

Van-Hieu Mai, Hyun-Su Koo, Jorge-Eduardo Ponce-Zea, Jin-Pyo An, Thuong T. T. Nguyen, Hyang Burm Lee*, Hyung-Sik Kang* and Won-Keun Oh*,

{"title":"Dereplication of Sesquiterpene-Proline Conjugates and Phenalenones from Penicillium sp. CNUFC-EML-48 Using Molecular Networking and Cytotoxicity Profiling","authors":"Van-Hieu Mai, Hyun-Su Koo, Jorge-Eduardo Ponce-Zea, Jin-Pyo An, Thuong T. T. Nguyen, Hyang Burm Lee*, Hyung-Sik Kang* and Won-Keun Oh*, ","doi":"10.1021/acs.jnatprod.5c00630","DOIUrl":"10.1021/acs.jnatprod.5c00630","url":null,"abstract":"The use of feature-based molecular networking (FBMN) for metabolomic analysis of the fungal strain Penicillium sp. CNUFC-EML-48 resulted in the isolation of 17 secondary metabolites. These included four new sesquiterpene-proline conjugates, aculenamides A-D (1–4), and six new phenalenones (9–14). The chemical structures of the isolated compounds were elucidated through extensive spectroscopic analyses, using 1D and 2D NMR, electronic circular dichroism (ECD), and MS/MS fragmentation analysis. Compounds 1-4 possessed a rare sesquiterpene-amino acid scaffold incorporating a proline moiety, and the natural occurrence of this structural motif was confirmed through the semisynthesis of compound 1. The cytotoxic effects of compounds 1-17 were evaluated in MC38 murine colorectal cancer cells. Among them, compounds 9–11 and 17 significantly inhibited cancer cell proliferation. Notably, compound 17 showed an antiproliferative effect by inducing S-phase cell cycle arrest, which was accompanied by upregulation of the tumor suppressor proteins p53 and p27. Furthermore, treatment with compound 17 markedly increased intracellular reactive oxygen species (ROS) levels, suggesting that ROS-mediated oxidative stress may contribute to the induction of cell cycle arrest in MC38 cells. Collectively, these findings support the potential of compound 17 as a cell cycle–modulating scaffold for the treatment of colorectal cancer.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 8","pages":"1958–1969"},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726005","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

Sonnerachromones A–G, Antiaging Chromones from the Fruit of Mangrove Sonneratia apetala 无瓣海桑果实中的抗衰老色素A-G。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-28 DOI: 10.1021/acs.jnatprod.5c00673

Jia-Lang Xia, Jian-Yun Liu, Kai Liu, Yue-Yao Li, Meng Bai*, Cheng-Hai Gao* and Xiang-Xi Yi*,

{"title":"Sonnerachromones A–G, Antiaging Chromones from the Fruit of Mangrove Sonneratia apetala","authors":"Jia-Lang Xia, Jian-Yun Liu, Kai Liu, Yue-Yao Li, Meng Bai*, Cheng-Hai Gao* and Xiang-Xi Yi*, ","doi":"10.1021/acs.jnatprod.5c00673","DOIUrl":"10.1021/acs.jnatprod.5c00673","url":null,"abstract":"Seven novel chromone derivatives, sonnerachromones A–G (1–7), were isolated from the fruit of mangrove Sonneratia apetala. Compounds 1–3 contain a 6/5/6/6/tetracyclic system with rare C-glycosyl spirocyclic skeletons. The unusual structures were identified by analysis of HRESIMS data, NMR spectra, electronic circular dichroism (ECD), DFT-calculated 13C NMR chemical shifts, DP4plus probability analysis, and single-crystal X-ray diffraction. The lifespan-extending activity of compounds 1–7 was evaluated using the worm Caenorhabditis elegans model. All compounds significantly protected C. elegans by extending its lifespan (p < 0.01). Among these, compounds 1–3, featuring C-glycosyl spirocyclic skeletons, showed the most significant activity. Specifically, they extended the mean lifespan of C. elegans by up to 39.4, 27.5, and 35.8%, respectively. The maximum and mean survival times of compounds 1 and 3 were higher than those in the positive group. Additionally, compounds 1–7 can also be found to delay the age-related decline in pumping rates and bending function across different treatment durations. Among these, compound 1 exhibited the most pronounced effect, with a health span that was 23% longer than that of the blank control group and the maximum number of body bends reaching 108 ± 7.22.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 8","pages":"1980–1987"},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726008","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 of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ) 新的豆烷型三萜作为rar相关孤儿受体γ (RORγ)的拮抗激动剂的鉴定。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-28 DOI: 10.1021/acs.jnatprod.5c00416

Patrik F. Schwarz, Alexander F. Perhal, Famke Guder, Jorge Enrique Hernández González, Kerrin Janssen, Ece Sağıroğlu, Ammar Tahir, Johannes Kirchmair, Natacha Rochel, Verena M. Dirsch and Ya Chen*,

{"title":"Identification of New Lupane-Type Triterpenoids as Inverse Agonists of RAR-Related Orphan Receptor Gamma (RORγ)","authors":"Patrik F. Schwarz, Alexander F. Perhal, Famke Guder, Jorge Enrique Hernández González, Kerrin Janssen, Ece Sağıroğlu, Ammar Tahir, Johannes Kirchmair, Natacha Rochel, Verena M. Dirsch and Ya Chen*, ","doi":"10.1021/acs.jnatprod.5c00416","DOIUrl":"10.1021/acs.jnatprod.5c00416","url":null,"abstract":"Targeting retinoic acid-related orphan receptor γ (RORγ) with inverse agonists presents a promising therapeutic strategy for treating autoimmune diseases, including psoriasis, rheumatoid arthritis, and multiple sclerosis. Through structure-based virtual screening, we identified a lupane-type pentacyclic triterpenoid, (2Z)-2-(2-furanylmethylene)-3-oxolup-20(29)-en-28-oic acid (15), as a new inverse agonist of RORγ. The compound exhibited IC50 values of 0.4 μM and 0.9 μM in Gal4-RORγ and full-length RORγ luciferase assays, respectively. Compound 15 showed improved potency and efficacy compared to a structurally related known inverse agonist, betulinic acid. Among the four additional analogues tested (15.1-15.4), two (15.2 and 15.3) also demonstrated RORγ inverse agonist activity with low micromolar IC50 values in Gal4-RORγ luciferase assay. Real-time quantitative polymerase chain reaction experiments confirmed that compounds 15, 15.2, and 15.3 downregulated RORγ target genes. Thermal shift assays showed that both betulinic acid and 15 stabilized the RORγ ligand-binding domain. Molecular docking and structure–activity relationship analysis revealed distinct binding modes within the RORγ ligand-binding domains, further supported by site-directed mutagenesis. These findings expand the repertoire of RORγ inverse agonists based on the pentacyclic triterpenoid scaffolds.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 8","pages":"1887–1900"},"PeriodicalIF":3.6,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://pubs.acs.org/doi/pdf/10.1021/acs.jnatprod.5c00416","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726007","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

Tailoring of Prematurely Released Polyketide Intermediates in Piericidin Biosynthesis 吡虫啉生物合成中提前释放聚酮中间体的裁剪。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-27 DOI: 10.1021/acs.jnatprod.5c00609

Hattan A. Alharbi, Muhammad Amin, KH Ahammad Uz Zaman, Wei Zhou, Zhiran Ju and Taifo Mahmud*,

{"title":"Tailoring of Prematurely Released Polyketide Intermediates in Piericidin Biosynthesis","authors":"Hattan A. Alharbi, Muhammad Amin, KH Ahammad Uz Zaman, Wei Zhou, Zhiran Ju and Taifo Mahmud*, ","doi":"10.1021/acs.jnatprod.5c00609","DOIUrl":"10.1021/acs.jnatprod.5c00609","url":null,"abstract":"Piericidins make up a group of microbial-derived polyketide natural products with a wide variety of biological activities. Their biosynthetic gene clusters (BGCs) have been identified in several strains of Streptomyces. In Streptomyces pactum, the piericidin BGC splits into two loci consisting of genes that encode six modular (type I) polyketide synthases and five post polyketide synthase (PKS) modification enzymes. Here, we report that inactivation of the pieA5 gene of the piericidin PKS in a mutant strain of S. pactum, in which several other major biosynthetic pathways have been inactivated, led to the identification of four piericidin polyketide intermediates (1–4) that were offloaded prematurely from the PKS. Compounds 1–3 are derived from an isopropyl starter unit, whereas compound 4 is derived from an acetyl starter unit. Compounds 1 and 4 have a terminal carboxylic acid, whereas compounds 2 and 3 have a terminal amide and a pendant methyl group at C-2. Compound 3 also contains an epoxide ring in the polyketide chain. The results reveal the ability of the piericidin PKS to offload incomplete polyketide intermediates and uncover the highly promiscuous tailoring enzymes that can modify the prematurely released short chain polyketides.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 8","pages":"1928–1935"},"PeriodicalIF":3.6,"publicationDate":"2025-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726009","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

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Brodie W. Bulcock, Gavin R. Flematti and Samuele Sala*,

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Ángel D. Hernández-Mejías, Gabriel D. Jimenez-Nieves and Eduardo J. E. Caro-Diaz*,

引用次数: 0

Insights into the Biosynthesis of Kibdelomycin and Amycolamicin from Comparative Biosynthetic Gene Cluster Analysis and Precursor Incorporation Studies 从比较生物合成基因聚类分析和前体掺入研究对基德霉素和Amycolamicin生物合成的见解。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-07-25 DOI: 10.1021/acs.jnatprod.5c00726

Marina Sánchez-Hidalgo*, José Miguel Quesada, Daniel Oves-Costales, Jonah Fine, Jesús Martín, Fernando Román-Hurtado, Ryann Callaghan, Vanessa Raab, Jillian Scarpanito, John B. Perkins, Neal Connors, Vincent Gullo, Ryan D. Cohen, Benjamin Philmus, Sheo B. Singh* and Olga Genilloud,

{"title":"Insights into the Biosynthesis of Kibdelomycin and Amycolamicin from Comparative Biosynthetic Gene Cluster Analysis and Precursor Incorporation Studies","authors":"Marina Sánchez-Hidalgo*, José Miguel Quesada, Daniel Oves-Costales, Jonah Fine, Jesús Martín, Fernando Román-Hurtado, Ryann Callaghan, Vanessa Raab, Jillian Scarpanito, John B. Perkins, Neal Connors, Vincent Gullo, Ryan D. Cohen, Benjamin Philmus, Sheo B. Singh* and Olga Genilloud, ","doi":"10.1021/acs.jnatprod.5c00726","DOIUrl":"10.1021/acs.jnatprod.5c00726","url":null,"abstract":"Kibdelomycin and amycolamicin are identical antibiotics produced by Kibdelosporangium banguiense CA-240109 and Amycolatopsis sp. MK575-fF5, respectively. They are broad-spectrum antibiotics showing potent activity against antibiotic-resistant Gram-positive bacteria. These compounds inhibit DNA gyrase subunit B (GyrB) and topoisomerase IV (ParE) by a unique U-shaped multicontact binding mode and have no cross-resistance to known antibiotics. Kibdelomycin represents a promising scaffold for developing new antibiotics, but its poor production, structural complexity, and chemical stability limit its chemical modification. In this work, we describe the improvement of kibdelomycin production via strain mutagenesis and the elucidation of kibdelomycin biosynthesis using isotope-labeled feeding experiments and sequencing of the kibdelomycin and amycolamicin biosynthetic gene clusters (BGCs), which are similar but not identical. These studies provide avenues for structure-guided biosynthetic analogue development as well as material for chemical modification.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":"88 8","pages":"1988–1999"},"PeriodicalIF":3.6,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144705771","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

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Caroline van Haaften*, Jan Koek, Jaap D. H. van Eendenburg, Jim van Wiltenburg, Daphne J. F. Kluitmans, Yvonne Grobben, Guido J. R. Zaman* and Wolter ten Hoeve,

引用次数: 0

IF 3.3 2区生物学

Journal of Natural Products Pub Date : 2025-07-25

Shiwei Chen, Sarah Al Kinani, Oli Horyn, Colin Galliano, Era Srivastava, David C. Rowley, Kathryn M. Ramsey, Divita Mathur and Matthew J. Bertin*,

引用次数: 0