Journal of Natural Products 最新文献

Discovery and Biosynthesis of Cinnamoyl-Containing Pepticinnamins Q-V Produced by the Marine-Derived Streptomyces sp. SCSIO 68065. 海洋来源链霉菌sp. SCSIO 68065产生的含肉桂酰肽Q-V的发现和生物合成

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-10-02 DOI: 10.1021/acs.jnatprod.5c00991

Zeping Chen, Sihui Bian, Zhenye Yang, Xiaoyi Wei, Qinglian Li, Changli Sun, Zhuo Shang, Jianhua Ju, Shaobin Fu, Junying Ma

{"title":"Discovery and Biosynthesis of Cinnamoyl-Containing Pepticinnamins Q-V Produced by the Marine-Derived Streptomyces sp. SCSIO 68065.","authors":"Zeping Chen, Sihui Bian, Zhenye Yang, Xiaoyi Wei, Qinglian Li, Changli Sun, Zhuo Shang, Jianhua Ju, Shaobin Fu, Junying Ma","doi":"10.1021/acs.jnatprod.5c00991","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00991","url":null,"abstract":"Guided by comprehensive bioinformatic analysis and global molecular networking, four previously undescribed peptidic natural products, pepticinnamins Q-T (1-4), along with two known analogues (5, 6), were isolated from cultures of the marine-derived Streptomyces sp. SCSIO 68065. Heterologous expression of the pcn biosynthetic gene cluster in the engineered chassis strain Streptomyces atratus ZH16NSEPK enabled the production of pepticinnamin analogues and led to the targeted isolation of two undescribed biosynthetic intermediates, pepticinnamins U and V (7, 8), as well as the known compound pepticinnamin M (9). The structures of these compounds were elucidated by spectroscopic analyses (including 1D and 2D NMR), HRESIMS, time-dependent density functional theory electronic circular dichroism (TDDFT-ECD) calculations, single-crystal X-ray diffraction studies, and advanced Marfey's method. Pepticinnamins Q-S (1-3) and U (7) are characterized by an unusual epoxidized cinnamoyl moiety. Comparative genomic analysis with homologous gene clusters allowed the proposal of their plausible biosynthetic pathways. Moreover, the cytochrome P450 monooxygenase Pcn29 was experimentally confirmed to catalyze the key epoxidation of the cinnamoyl moiety through a combination of targeted gene deletion and in vitro enzymatic reconstitution studies.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145204989","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

Eleusenticosides A-O: Neuroprotective Triterpenoid Saponins from the Leaves of Eleutherococcus senticosus Using a Building-Block-Based Molecular Networking Strategy. 利用基于构建块的分子网络策略从刺痛绦虫叶片中提取神经保护三萜皂苷a - o。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-10-01 DOI: 10.1021/acs.jnatprod.5c00763

Yu Zhou, Xi-Tao Li, Pu-Pei Chen, Wen-Jie Luo, Ying-Shan Ren, Jie-Chun Zhou, Hui-Lin Li, Yu-Hong Huang, Yu-Hang Wu, Xiu-Hong Piao, Zhi-You Yang, Katsuko Komatsu, Hui-Min Gao, Yue-Wei Ge

{"title":"Eleusenticosides A-O: Neuroprotective Triterpenoid Saponins from the Leaves of Eleutherococcus senticosus Using a Building-Block-Based Molecular Networking Strategy.","authors":"Yu Zhou, Xi-Tao Li, Pu-Pei Chen, Wen-Jie Luo, Ying-Shan Ren, Jie-Chun Zhou, Hui-Lin Li, Yu-Hong Huang, Yu-Hang Wu, Xiu-Hong Piao, Zhi-You Yang, Katsuko Komatsu, Hui-Min Gao, Yue-Wei Ge","doi":"10.1021/acs.jnatprod.5c00763","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00763","url":null,"abstract":"Twenty-two oleanane-type triterpenoid saponins were isolated from the ethanol-extract of Eleutherococcus senticosus leaves through building-block-based molecular-networking-guided strategy, among which 15 new compounds, eleusenticosides A-O (1-15), were isolated and identified. Notably, eleusenticosides A and B (1, 2) containing eight sugar units were the largest saponins that have been discovered from E. senticosus so far. The structural elucidation was achieved using comprehensive spectroscopic techniques, including 1D/2D NMR and HRESIMS, complemented by acid hydrolysis. Furthermore, the neuroprotective potential of these saponins was evaluated in an Aβ25-35-induced neurite degeneration primary neuron model. The results revealed that saponins 3, 5, 17 and 19 can significantly restrain the axonal damage and promote neuronal network regeneration, suggesting their potential as therapeutic candidates for neurodegenerative diseases. A structure-activity relationship analysis mainly revealed that the neuroprotectivity of saponins might be affected mainly by the noroleanane-type aglycone and specific sugar units.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197562","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

Ufisonitriles A and B, Antimalarial Isonitriles with Mitochondrial Function Inhibitory Activity Produced by Amycolatopsis sp. OK19-0009. Amycolatopsis sp. OK19-0009产生的具有线粒体功能抑制活性的抗疟异腈化合物A和B。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-30 DOI: 10.1021/acs.jnatprod.5c00824

Emi Arakawa, Yoshihiro Watanabe, Hayama Tsutsumi, Akari Ikeda, Tomoyasu Hirose, Noriko Sato, Takumi Chinen, Akira Také, Hiroki Kanto, Yuki Inahashi, Takahiro Ishii, Toshiaki Teruya, Toshiaki Sunazuka, Hideaki Hanaki, Takeo Usui, Rei Hokari, Aki Ishiyama, Yukihiro Asami, Masato Iwatsuki

{"title":"Ufisonitriles A and B, Antimalarial Isonitriles with Mitochondrial Function Inhibitory Activity Produced by Amycolatopsis sp. OK19-0009.","authors":"Emi Arakawa, Yoshihiro Watanabe, Hayama Tsutsumi, Akari Ikeda, Tomoyasu Hirose, Noriko Sato, Takumi Chinen, Akira Také, Hiroki Kanto, Yuki Inahashi, Takahiro Ishii, Toshiaki Teruya, Toshiaki Sunazuka, Hideaki Hanaki, Takeo Usui, Rei Hokari, Aki Ishiyama, Yukihiro Asami, Masato Iwatsuki","doi":"10.1021/acs.jnatprod.5c00824","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00824","url":null,"abstract":"Two novel antimalarials, named ufisonitriles A (1) and B (2), were isolated by bioassay-guided fractionation on mitochondrial function inhibitory activity using multidrug-sensitive budding yeast from the cultured broth of the Okinawan rare actinomycete Amycolatopsis sp. OK19-0009 strain. Their structures were comprehensively elucidated using HR-ESI-MS and 1D/2D NMR analyses and the modified Mosher's method. Structurally, 1 and 2 possess a novel skeleton with an isocyano group. In vitro antimalarial evaluation against Plasmodium falciparum strains revealed that 1 and 2 exhibited moderate activity with IC50 values ranging from 28.6 to 1.12 μM. Furthermore, 1 and 2 reduced the malaria parasites by approximately 45% in vivo on intraperitoneal administration (30 mg/kg/day for 4 days) with no observed toxicity. We also provide a plausible biosynthesis pathway based on the genome sequence analysis.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190477","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

Discovery and Characterization of a cis-Casbene Diterpene Synthase from Streptomyces paromomycinus. 巨巨链霉菌中顺式casbene二萜合成酶的发现和鉴定。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-30 DOI: 10.1021/acs.jnatprod.5c00870

Xinru Sun, Fang-Ru Li, Qian Yang, Xingming Pan, Hui-Min Xu, Liao-Bin Dong

{"title":"Discovery and Characterization of a cis-Casbene Diterpene Synthase from Streptomyces paromomycinus.","authors":"Xinru Sun, Fang-Ru Li, Qian Yang, Xingming Pan, Hui-Min Xu, Liao-Bin Dong","doi":"10.1021/acs.jnatprod.5c00870","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00870","url":null,"abstract":"Casbene-type diterpenoids are important bioactive natural products, but all known examples possess exclusively trans-configured double bonds. Here, we report the discovery of SpTS1 from Streptomyces paromomycinus, a diterpene synthase that produces the first naturally occurring cis-casbene. Through heterologous expression and in vitro characterization, we isolated four novel cis-diterpenes from the substrate nerylneryl diphosphate (NNPP): (1S,2Z,6Z,10Z,14S)-casbene (1) featuring the characteristic bicyclo[12.1.0]pentadecane scaffold, 14-membered macrocyclic diterpene 2, and two monocyclic diterpenes 3 and 4. The absolute configurations of 1 and 2 were established through ECD spectroscopy and quantum calculations. Notably, SpTS1 also accepts trans-substrate geranylgeranyl diphosphate (GGPP) to produce cembrene-type diterpenes, demonstrating unusual substrate promiscuity. This discovery not only fills an important gap in casbene natural product diversity but also reveals new possibilities for engineering stereochemically diverse terpenoids.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145197517","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

Hygromycin B Is a Highly Versatile Inducer of Secondary Metabolite Production Applicable Across Diverse Fungal Taxa. 潮霉素B是一种高度通用的次生代谢产物诱导剂，适用于不同真菌分类群。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-30 DOI: 10.1021/acs.jnatprod.5c00770

Sho Kato, Yoshihiro Watanabe, Hiroki Kojima, Yuta Kikuchi, Mika Watabe, Yuki Hayashi, Ryoya Ibuki, Hayama Tsutsumi, Yuki Inahashi, Kenichi Nonaka, Masato Iwatsuki

{"title":"Hygromycin B Is a Highly Versatile Inducer of Secondary Metabolite Production Applicable Across Diverse Fungal Taxa.","authors":"Sho Kato, Yoshihiro Watanabe, Hiroki Kojima, Yuta Kikuchi, Mika Watabe, Yuki Hayashi, Ryoya Ibuki, Hayama Tsutsumi, Yuki Inahashi, Kenichi Nonaka, Masato Iwatsuki","doi":"10.1021/acs.jnatprod.5c00770","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00770","url":null,"abstract":"Hygromycin B, a well-known antibiotic agent, was recently reported as an inducer of secondary metabolites for a fungal strain of Fusarium sp. In this study, we verified the versatility and usefulness of hygromycin B as an inducer of fungal secondary metabolite production. We demonstrate that hygromycin B induces the production of various fungal secondary metabolites, including polyketides, peptides, and terpenes, in 71% of 28 fungal strains belonging to the Ascomycota phylum, specifically within the Eurotiomycetes, Sordariomycetes, and Dothideomycetes classes. We also demonstrate the discovery of novel compounds, named hannocateol (1) and shirazines A (2) and B (3), from the hygromycin B-supplemented cultured materials. The production of the novel compounds increased with hygromycin B-supplementation up to 100 μg/g (maximum >100-fold) but not by HDAC inhibitors, protein synthesis inhibitors against prokaryotes, and antifungal agents. Notably, protein synthesis inhibitors against eukaryotes similar to hygromycin B, such as 5-fluorouracil and paromomycin, could induce the production of 1 and 2, suggesting that its mechanism would be associated with protein synthesis inhibition. We proved that hygromycin B is a highly versatile inducer of secondary metabolite production applicable across diverse fungal taxa, making it a simple and powerful tool for uncovering cryptic biosynthetic pathways and discovering novel bioactive compounds.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145190380","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

Angucystemycins, Highly Oxygenated Acetylcysteine-Angucycline Hybrid Conjugates Derived from a Soil Metagenomic Library. 从土壤宏基因组文库中获得的高氧乙酰半胱氨酸-安古霉素杂合物。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-27 DOI: 10.1021/acs.jnatprod.5c00642

Ruijie Huang, Dan Yang, Qingqing Ji, Lishuang Nie, Yunbin Lyu, Shaochen Wang, Liyan Wang, Zhiyang Feng

{"title":"Angucystemycins, Highly Oxygenated Acetylcysteine-Angucycline Hybrid Conjugates Derived from a Soil Metagenomic Library.","authors":"Ruijie Huang, Dan Yang, Qingqing Ji, Lishuang Nie, Yunbin Lyu, Shaochen Wang, Liyan Wang, Zhiyang Feng","doi":"10.1021/acs.jnatprod.5c00642","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00642","url":null,"abstract":"A type II polyketide biosynthetic gene cluster (agc) was identified from a soil metagenomic library. The gene cluster harbors several distinct oxidoreductase genes, suggesting that the heterologous expression of the agc gene cluster could yield novel polycyclic aromatic polyketides featuring unique redox-driven modifications. Eight angucycline derivatives were isolated from Streptomyces albus J1074 harboring the agc gene cluster, including two new S-bridged acetylcysteine-angucycline compounds, angucystemycins (1-2), a new angucycline congener, emycin H (3), along with five known analogues, rubiginone B2 (4), emycin C (5), rubiginone B1 (6), ochromycinone (7), and emycin A (8). Their structures were elucidated based on detailed High-Resolution Electrospray Ionization Mass Spectrometry and 1D and 2D NMR spectroscopy. The proposed biosynthetic pathway of angucystemycins indicated that the angucycline core and the acetylcysteine moiety are derived from the agc biosynthetic gene cluster and S. albus J1074, respectively. In addition, emycin H (3) and emycin C (5) exhibited inhibitory activity against Bacillus subtilis 168 and B. pumilus CMCC 63202. Structural analysis suggested that the saturated bond between C-5 and C-6 contributes to the activity, whereas the introduction of a C-8 O-methyl group diminishes the antimicrobial activity of the compounds of this structural class, implying a potential structure-activity relationship.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145181753","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 Elucidation of Purpurinidin from Salix purpurea Reveals an Undescribed Class of Pyranoanthocyanins─the Salicinocyanins. 杨柳紫花苷的结构解析揭示了一类未被描述的Pyranoanthocyanins - salicinoyanins。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-26 DOI: 10.1021/acs.jnatprod.5c00599

Philipp Hopfstock, Mario Simirgiotis, Peter Winterhalter, Recep Gök

{"title":"Structure Elucidation of Purpurinidin from Salix purpurea Reveals an Undescribed Class of Pyranoanthocyanins─the Salicinocyanins.","authors":"Philipp Hopfstock, Mario Simirgiotis, Peter Winterhalter, Recep Gök","doi":"10.1021/acs.jnatprod.5c00599","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00599","url":null,"abstract":"Plants from the family Salicaceae have been used as health-promoting products for more than 3,500 years. They contain various secondary metabolites such as anthocyanins and phenolic glycosides (salicinoids) derived from salicin, a prodrug of salicylic acid, one of the most commonly used drugs today. Anthocyanins, which are primarily found in berries and certain vegetables, are recognized for their wide range of health benefits. Although salicinoids are well-known, knowledge regarding the occurrence of anthocyanins in this plant family is limited. In the early 1970s, Bridle et al. discovered an unknown anthocyanin in the bark of Salix purpurea, which was named purpurinidin. As far as we know, however, the structure of purpurinidin has not been elucidated to date. In this work, we present the isolation and structure elucidation of compound 1 that we suspect to be the aforementioned purpurinidin, which reveals the existence of new group of anthocyanin- and salicinoid-derived pyranoanthocyanin-type compounds. We have named this new type of pyranoanthocyanins \"salicinocyanins\" to emphasize their chemical origins.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147219","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

Isolation and Structure Elucidation of Uric Acid Lowering Lipopeptides from an Okeania sp. Marine Cyanobacterium. 海洋蓝藻降尿酸脂肽的分离与结构分析。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-26 DOI: 10.1021/acs.jnatprod.5c01074

Sein Higa, Kazumasa Yagisawa, Noriyuki Natsume, Naoaki Kurisawa, Kiyotake Suenaga, Toshiaki Teruya

引用次数: 0

Complex Chalcone Scaffolds from Mallotus philippinensis Fruits as Potential iNOS Inhibitors. 菲律宾马柳果实查尔酮复合物作为潜在的iNOS抑制剂。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-25 DOI: 10.1021/acs.jnatprod.5c00739

Yen Thi Hoang Kieu, Hiroyuki Hattori, Masako Toda, Emiko Yanase

{"title":"Complex Chalcone Scaffolds from Mallotus philippinensis Fruits as Potential iNOS Inhibitors.","authors":"Yen Thi Hoang Kieu, Hiroyuki Hattori, Masako Toda, Emiko Yanase","doi":"10.1021/acs.jnatprod.5c00739","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00739","url":null,"abstract":"The chalcone skeleton is a fundamental structural motif in numerous natural and synthetic compounds, playing a crucial role in various biological activities, including anticancer and anti-inflammatory effects. Mallotus philippinensis is a remarkable source of chalcones, recognized for its diverse chemical structures and significant bioactivity. The presence of complex dimeric chalcones in this species is both characteristic and rare. However, to the best of our knowledge, only five such complex dimeric chalcones have been identified to date. Here, we report six novel complex chalcones, runachalcones A-F (1-6), which significantly expand the chemical space of dimeric chalcones and highlight the untapped structural diversity within M. philippinensis fruits. Their planar structures were elucidated using a combination of NMR spectroscopy and HR-ESIMS, while their absolute configurations were determined through J-based configurational analysis, ROESY spectra, and quantum mechanical calculations of ECD. In an assay using a macrophage line RAW 264.7, only runachalcone F suppressed lipopolysaccharide (LPS)-induced expression of inducible nitric oxide synthase (iNOS) protein and the production of nitric oxide, suggesting that the compound possesses potential anti-inflammatory properties.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145135954","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

A Dual-Target-Based Screening Strategy for Anti-SARS-CoV-2 Active Compounds Enabling the Identification of Macrocyclic Peptide Natural Products: Chloropeptins. 基于双靶点的抗sars - cov -2活性化合物筛选策略，可鉴定大环肽天然产物：氯霉素。

IF 3.6 2区生物学

Journal of Natural Products Pub Date : 2025-09-25 DOI: 10.1021/acs.jnatprod.5c00634

Aoi Kimishima, Terumasa Ikeda, Otowa Takahashi, Kamrun Naher, Chiduru Watanabe, Reiko Takai-Todaka, Kei Haga, Sota Honma, Yukiko Ujie, Takayuki Uematsu, Masako Honsho, Toshiaki Sunazuka, Teruki Honma, Kazuhiko Katayama, Yukihiro Asami

{"title":"A Dual-Target-Based Screening Strategy for Anti-SARS-CoV-2 Active Compounds Enabling the Identification of Macrocyclic Peptide Natural Products: Chloropeptins.","authors":"Aoi Kimishima, Terumasa Ikeda, Otowa Takahashi, Kamrun Naher, Chiduru Watanabe, Reiko Takai-Todaka, Kei Haga, Sota Honma, Yukiko Ujie, Takayuki Uematsu, Masako Honsho, Toshiaki Sunazuka, Teruki Honma, Kazuhiko Katayama, Yukihiro Asami","doi":"10.1021/acs.jnatprod.5c00634","DOIUrl":"https://doi.org/10.1021/acs.jnatprod.5c00634","url":null,"abstract":"Toward the development of innovative antiviral drugs, potential dual inhibitors were screened from the O̅mura natural compound library by the use of SARS-CoV-2 3CLpro enzyme activity and SARS-CoV-2 spike trimer-ACE2 ELISA assays. This screening identified macrocyclic peptide natural products, chloropeptins, as potential dual inhibitors. Further evaluation of their anti-SARS-CoV-2 activity against several variants demonstrated their strong potency (IC50 = 2.96-4.36 μM). Pseudovirus and BlaM-Vpr assays utilizing SARS-CoV-2 spike pseudovirus confirmed that chloropeptin 1 effectively blocks viral entry. Additionally, molecular docking simulations revealed that chloropeptins form hydrogen bonds and van der Waals interactions with Lys353 and His34 of ACE2, implicating key roles involved in SARS-CoV-2 spike protein binding. These findings highlight chloropeptins as promising candidates for the development of novel anti-SARS-CoV-2 therapeutics.","PeriodicalId":47,"journal":{"name":"Journal of Natural Products ","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145147135","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