Marine Drugs最新文献

{"title":"Bioactive Terpenes from Marine Sponges and Their Associated Organisms.","authors":"Yuan Yuan, Yu Lei, Muwu Xu, Bingxin Zhao, Shihai Xu","doi":"10.3390/md23030096","DOIUrl":"10.3390/md23030096","url":null,"abstract":"<p><p>In recent years, marine natural products have continued to serve as a pivotal resource for novel drug discovery. Globally, the number of studies focusing on Porifera has been on the rise, underscoring their considerable importance and research value. Marine sponges are prolific producers of a vast array of bioactive compounds, including terpenes, alkaloids, peptides, and numerous secondary metabolites. Over the past fifteen years, a substantial number of sponge-derived terpenes have been identified, exhibiting extensive structural diversity and notable biological activities. These terpenes have been isolated from marine sponges or their associated symbiotic microorganisms, with several demonstrating multifaceted biological activities, such as anti-inflammatory, antibacterial, cytotoxic, anticancer, and antioxidant properties. In this review, we summarize 997 novel terpene metabolites, detailing their structures, sources, and activities, from January 2009 to December 2024. The structural features and structure-activity relationship (SAR) of different types of terpenes are broadly analyzed and summarized. This systematic and comprehensive review will contribute to the summary of and speculation on the taxonomy, activity profiles, and SAR of terpenes and the development of sponge-derived terpenes as potential lead drugs.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943499/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Advancements of Marine Natural Products in the Treatment of Alzheimer's Disease: A Study Based on Cell and Animal Experiments.","authors":"Chunbo Jia, Jiaxin Chai, Shenyun Zhang, Yining Sun, Liheng He, Zhipei Sang, Dapeng Chen, Xu Zheng","doi":"10.3390/md23030091","DOIUrl":"10.3390/md23030091","url":null,"abstract":"<p><p>As life expectancy rises and the aging population grows, Alzheimer's disease (AD) has become a significant global health concern. AD is a complex neurodegenerative disorder with an unclear etiology. Current hypotheses primarily focus on β-amyloid (Aβ) aggregation, tau protein hyperphosphorylation, and neuroinflammation as key pathological processes. Given the limited efficacy of existing therapeutic strategies, there is an urgent need to explore novel treatment options. Marine natural products have garnered significant attention due to their unique chemical structures and diverse bioactivities, demonstrating potential for multi-target interventions in AD. This review systematically summarizes the roles of marine-derived compounds, including polysaccharides, carotenoids, and polyphenols, in modulating Aβ aggregation, mitigating tau protein pathology, and regulating gut-brain axis dysfunction. Furthermore, the challenges of current research are discussed, with an emphasis on improving blood-brain barrier permeability and optimizing drug delivery systems to facilitate clinical translation.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943648/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Steroidal FXR Agonistic Dimeric 2-Methyl-4-(1-glycerol)furan with Lipid-Lowering Activities from Marine-Derived <i>Nocardiopsis</i> sp. ZSN1.","authors":"Yongjun Jiang, Zhen Lei, Jiebin Fang, Yanping Wu, Chengpeng Sun","doi":"10.3390/md23030092","DOIUrl":"10.3390/md23030092","url":null,"abstract":"<p><p>Five novel 2-methyl-4-(1-glycerol)furan (MGF) dimers, namely nocardifuran A (<b>1</b>), 13-<i>acetyl</i>-nocardifuran A (<b>2</b>), 15-<i>epi</i>-nocardifuran A (<b>3</b>), nocardifuran B (<b>4</b>), and nocardifuran C (<b>5</b>), were isolated from the Gause liquid fermentation of the marine-derived <i>Nocardiopsis</i> sp. ZSN1. Their structures were elucidated through HRESIMS, 1D and 2D NMR spectroscopic data analysis, and ECD calculations. Compounds <b>1</b>-<b>4</b> were identified as derivatives of MGF with its rearrangement of furan or pyran derivatives, while compound <b>5</b> was identified as the derivative of MGF with an indole derivative. These MGF dimers, representing a new structural class, were isolated from a marine microorganism for the first time, thereby enhancing chemical diversity. Screening for farnesoid X receptor (FXR) agonistic activity revealed that MGF dimers could activate FXR. Furthermore, bioactivity evaluations demonstrated that these types of compounds exhibited lipid-lowering activity with lower cytotoxicity in vitro. Consequently, our findings not only contribute to the chemical diversity of marine-derived MGF-type natural products but also offer potential insights into the development of MGF dimers as lead compounds for FXR agonists in the dysregulation of hepatic lipid metabolism.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11944181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Impact of Chitinase Binding Domain Truncation on the Properties of <i>Ca</i>Chi18B from <i>Chitinilyticum aquatile</i> CSC-1.","authors":"Chenxi Gu, Jianrong Chen, Xinyue Huang, Yongqiang Jiang, Na Ou, Dengfeng Yang, Mingguo Jiang, Lixia Pan","doi":"10.3390/md23030093","DOIUrl":"10.3390/md23030093","url":null,"abstract":"<p><p>The chitinase binding domain (ChBD) plays a crucial role in the properties of enzymes. To assess its impact, we cloned a truncated mutant of the chitinase gene <i>CaChi18B</i> from the novel chitinase-producing facultative anaerobic bacterium <i>Chitinilyticum aquatile</i> CSC-1, designated as <i>CaChi18B_ΔChBD_s</i>. The recombinant chitinase was successfully expressed and purified, exhibiting a specific activity of 3.48 U/mg on colloidal chitin, with optimal conditions at 45 °C and pH 6.0, and retaining over 80% activity at temperatures up to 40 °C. Kinetic analysis revealed that the <i>K_m</i> value was 1.159 mg mL^-1 and the <i>V_max</i> was 10.37 μM min^-1 mg^-1. Compared to <i>Ca</i>Chi18B_ΔChBD₁, which has only the first ChBD truncated at the N-terminus, <i>Ca</i>Chi18B_ΔChBD_s exhibited minor changes in the optimal temperature and pH, while the <i>K_m</i> and <i>V_max</i> values increased significantly. <i>Ca</i>Chi18B_ΔChBD_s exhibited tolerance to various metal ions, with K⁺ and NH₄⁺ enhancing activity, while Cu²⁺ significantly inhibited it. Most organic reagents had minimal impact, except for formic acid, which severely reduced activity. The primary hydrolysis product in the initial phase was GlcNAc, contrasting with (GlcNAc)₂ for <i>Ca</i>Chi18B_ΔChBD₁. These findings indicated that the ChBD influences the enzyme's <i>K_m</i>, <i>V_max</i>, and product distribution, enhancing our understanding of ChBD's roles and advancing chitin utilization.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-Neuroinflammatory Eremophilane Sesquiterpenoids from Marine-Derived Fungus <i>Phoma</i> sp. DXH009.","authors":"Guanyu Yang, Mengwei Qin, Mingbin Chen, Yujia Shi, Siyi Liu, Yong Rao, Ling Huang, Ying Fu","doi":"10.3390/md23030094","DOIUrl":"10.3390/md23030094","url":null,"abstract":"<p><p>Three new eremophilane sesquiterpenoids (<b>1</b>-<b>3</b>), together with six known analogues, were isolated from the marine-derived fungus <i>Phoma</i> sp. DXH009. Their structures were elucidated through detailed NMR and MS spectroscopic analysis, and the absolute configurations of <b>1</b>-<b>4</b> were determined by conformational analysis and quantum chemical TDDFT-ECD calculation. Their anti-neuroinflammatory activities were evaluated using the lipopolysaccharide (LPS)-induced BV2 microglial cells. The results indicated that compound <b>5</b> (dihydrosporogen AO-1) exhibited significant inhibitory effects on the production of nitric oxide (NO) levels (EC₅₀ = 3.11 μM) with less cytotoxicity, leading to a reversal effect in inducing microphage polarization in LPS-treated BV2 microglial cells. These were correlated with suppressions of the canonical NF-κB pathway as well as the expression levels of key neuroinflammatory markers, including COX2, TNF-α, IL-6, and IL-1β. Correspondingly, treating <b>5</b> in LPS-induced mice efficiently ameliorated neuroinflammation in the tissues of the cortex and hippocampus. These findings suggest that eremophilane sesquiterpenoid <b>5</b> could be a potential candidate for the development of anti-neuroinflammatory drugs.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 3","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11943946/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143709910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzymatic Preparation of Carrageenan Oligosaccharides and Evaluation of the Effects on Growth Performance, Serum Biochemical Parameters and Non-Specific Immunity of <i>Crucian carp</i>.","authors":"Limin Ning, Zilong Guo, Benwei Zhu","doi":"10.3390/md23020090","DOIUrl":"10.3390/md23020090","url":null,"abstract":"<p><p>Carrageenan oligosaccharides (COSs) possess versatile activities and have drawn increasing attention in recent years. Due to their unique structures, COSs have been considered to be potential antibacterial agents and immune stimulators. Herein, we aimed to efficiently prepare the COSs by using a novel carrageenase CgkA from <i>Zobellia uliginosa</i> with high activity and further investigate the effects of dietary supplementation with COSs on the growth performance, serum biochemical parameters and non-specific immunity in Carassius auratus gibelio. The results indicated that the CgkA could effectively degrade the carrageenan into oligosaccharides with DPs of 2-6 and the oligosaccharides exhibited promoting effects on growth performance, serum biochemical index and non-specific immune parameters. After a 6-month feeding trial, the SR (Survival Ratio) was significantly higher in fish fed 0.1% (Diet 1), 0.2% (Diet 2), 0.5% (Diet 3) and 1% (Diet 4) COSs diets than that in the control group (<i>p</i> < 0.05). In addition, the supplementation of COSs decreased the malondialdehyde (MDA) content in the serum and increased the activity of lysozyme (LZM), superoxide dismutase (SOD) and catalase (CAT). In conclusion, COSs as a dietary supplement enhance the growth performance and non-specific immunity of crucian carp and their resistance to diseases.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857235/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Living Coral Displays, Research Laboratories, and Biobanks as Important Reservoirs of Chemodiversity with Potential for Biodiscovery.","authors":"Ricardo Calado, Miguel C Leal, Ruben X G Silva, Mara Borba, António Ferro, Mariana Almeida, Diana Madeira, Helena Vieira","doi":"10.3390/md23020089","DOIUrl":"10.3390/md23020089","url":null,"abstract":"<p><p>Over the last decades, bioprospecting of tropical corals has revealed numerous bioactive compounds with potential for biotechnological applications. However, this search involves sampling in natural reefs, and this is currently hampered by multiple ethical and technological constraints. Living coral displays, research laboratories, and biobanks currently offer an opportunity to continue to unravel coral chemodiversity, acting as \"Noah's Arks\" that may continue to support the bioprospecting of molecules of interest. This issue is even more relevant if one considers that tropical coral reefs currently face unprecedent threats and irreversible losses that may impair the biodiscovery of molecules with potential for new products, processes, and services. Living coral displays provide controlled environments for studying corals and producing both known and new metabolites under varied conditions, and they are not prone to common bottlenecks associated with bioprospecting in natural coral reefs, such as loss of the source and replicability. Research laboratories may focus on a particular coral species or bioactive compound using corals that were cultured <i>ex situ</i>, although they may differ from wild conspecifics in metabolite production both in quantitative and qualitative terms. Biobanks collect and preserve coral specimens, tissues, cells, and/or information (e.g., genes, associated microorganisms), which offers a plethora of data to support the study of bioactive compounds' mode of action without having to cope with issues related to access, standardization, and regulatory compliance. Bioprospecting in these settings faces several challenges and opportunities. On one hand, it is difficult to ensure the complexity of highly biodiverse ecosystems that shape the production and chemodiversity of corals. On the other hand, it is possible to maximize biomass production and fine tune the synthesis of metabolites of interest under highly controlled environments. Collaborative efforts are needed to overcome barriers and foster opportunities to fully harness the chemodiversity of tropical corals before in-depth knowledge of this pool of metabolites is irreversibly lost due to tropical coral reefs' degradation.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of MK8383s with Antifungal Activity from Mangrove Endophytic Fungi <i>Medicopsis</i> sp. SCSIO 40440 Against Fusarium Wilt of Banana.","authors":"Tianyu Zhou, Yulei Qiao, Lu Wang, Zifeng Li, Haibo Zhang, Liping Zhang, Shengrong Liao, Minhui Li, Changsheng Zhang, Wenjun Zhang","doi":"10.3390/md23020088","DOIUrl":"10.3390/md23020088","url":null,"abstract":"<p><p>Fusarium wilt of banana (FWB), caused by <i>Fusarium oxysporum</i> f. sp. <i>cubense</i> (<i>Foc</i>) tropical race 4 (TR4), poses a severe threat to the global banana industry. The screening of endophytic fungi from the mangrove plant led to the identification of <i>Medicopsis</i> sp. SCSIO 40440, which exhibited potent antifungal activity against Fusarium. The further fraction of the extract yielded ten compounds, including MK8383 (<b>1</b>) and nine new analogues, MK8383s B-J (<b>2</b>-<b>10</b>). The structures of <b>1</b>-<b>10</b> were elucidated using extensive spectroscopic data and single-crystal X-ray diffraction analysis. In vitro antifungal assays revealed that <b>1</b> showed strongly antifungal activities against Foc TR4, with an EC₅₀ of 0.28 μg/mL, surpassing nystatin and hygromycin B (32 and 16 μg/mL, respectively). Pot experiments showed that <b>1</b> or spores of SCSIO 40440 could significantly reduce the virulence of <i>Foc</i> TR4 on Cavendish banana.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492522","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marine Phytoplankton Bioactive Lipids and Their Perspectives in Clinical Inflammation.","authors":"Edoardo Andrea Cutolo, Rosanna Campitiello, Valeria Di Dato, Ida Orefice, Max Angstenberger, Maurizio Cutolo","doi":"10.3390/md23020086","DOIUrl":"10.3390/md23020086","url":null,"abstract":"<p><p>Marine phytoplankton is an emerging source of immunomodulatory bioactive lipids (BLs). Under physiological growth conditions and upon stress challenges, several eukaryotic microalgal species accumulate lipid metabolites that resemble the precursors of animal mediators of inflammation: eicosanoids and prostaglandins. Therefore, marine phytoplankton could serve as a biotechnological platform to produce functional BLs with therapeutic applications in the management of chronic inflammatory diseases and other clinical conditions. However, to be commercially competitive, the lipidic precursor yields should be enhanced. Beside tailoring the cultivation of native producers, genetic engineering is a feasible strategy to accrue the production of lipid metabolites and to introduce heterologous biosynthetic pathways in microalgal hosts. Here, we present the state-of-the-art clinical research on immunomodulatory lipids from eukaryotic marine phytoplankton and discuss synthetic biology approaches to boost their light-driven biosynthesis.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857744/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Statins Diversity Revealed by the Deep-Sea-Derived Fungus <i>Penicillium viridicatum</i>.","authors":"Meng Zhang, Rong Chao, Jia-Jian Wang, Zi-Han Xu, Ji-Hong Zhang, Da-Li Meng, Tai-Zong Wu, Xian-Wen Yang","doi":"10.3390/md23020087","DOIUrl":"10.3390/md23020087","url":null,"abstract":"<p><p>Seven new (<b>1</b>-<b>7</b>) and six known (<b>8</b>-<b>13</b>) statin derivatives were obtained from the deep-sea-derived fungus <i>Penicillium viridicatum</i> MCCC 3A00265. The structures assigned to the new compounds were based on a comprehensive analysis of the spectroscopic data, with absolute configurations established by Mosher analysis and biogenetic consideration. Most of the new compounds (<b>1</b>-<b>5</b> and <b>7</b>) share an octohydronaphthalene backbone, except that viridecalin F (<b>6</b>) possesses an uncommon naphthalene core. Viridecalins C (<b>3</b>) and F (<b>6</b>) and the two known compounds <b>9</b> and <b>11</b> exhibit considerable ability in reactivating mutant p53 protein at 10 μM, while viridecalin C showcases the most potent reactivation activity, indicating the potential of application in cancer therapy.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 2","pages":""},"PeriodicalIF":4.9,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11857571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143492616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}