Toxin-antitoxin (TA) systems, ubiquitous in bacterial and archaeal genomes, play pivotal roles in responding to environmental stresses, forming biofilms, defending against phages, and influencing pathogen virulence. The marine environment harbors Earth's most diverse and abundant microbial communities, where microorganisms have evolved unique genetic adaptations and specialized metabolic processes to thrive amid distinct environmental challenges. Research on the presence and function of TA systems in marine bacteria lags significantly behind that in model bacteria and pathogens. Here, we explored the diversity of the TA system in marine bacteria, including species from the Global Ocean Microbiome Catalogue (GOMC) and the Mariana Trench Environment and Ecology Research (MEER) databases. Our findings revealed that types I to VII (featuring protein toxins) of eight types of TA systems are prevalent in these microorganisms, with unidentified TA combinations diverging from previously characterized systems. Interestingly, some toxins or antitoxins lack canonical counterparts, indicating evolutionary divergence. Additionally, previously uncharacterized potential TA systems have been identified in extremophilic bacteria from the deep-sea Mariana Trench. These results highlight the adaptive importance of marine TA systems, which are likely operating through unconventional mechanisms.
{"title":"The Prevalence and Diversity of Marine Toxin-Antitoxin Systems.","authors":"Cong Liu, Yunxue Guo, Jiayu Gu, Zhen Wei, Pengxiang Chen, Xiaoxue Wang","doi":"10.3390/md23110436","DOIUrl":"10.3390/md23110436","url":null,"abstract":"<p><p>Toxin-antitoxin (TA) systems, ubiquitous in bacterial and archaeal genomes, play pivotal roles in responding to environmental stresses, forming biofilms, defending against phages, and influencing pathogen virulence. The marine environment harbors Earth's most diverse and abundant microbial communities, where microorganisms have evolved unique genetic adaptations and specialized metabolic processes to thrive amid distinct environmental challenges. Research on the presence and function of TA systems in marine bacteria lags significantly behind that in model bacteria and pathogens. Here, we explored the diversity of the TA system in marine bacteria, including species from the Global Ocean Microbiome Catalogue (GOMC) and the Mariana Trench Environment and Ecology Research (MEER) databases. Our findings revealed that types I to VII (featuring protein toxins) of eight types of TA systems are prevalent in these microorganisms, with unidentified TA combinations diverging from previously characterized systems. Interestingly, some toxins or antitoxins lack canonical counterparts, indicating evolutionary divergence. Additionally, previously uncharacterized potential TA systems have been identified in extremophilic bacteria from the deep-sea Mariana Trench. These results highlight the adaptive importance of marine TA systems, which are likely operating through unconventional mechanisms.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604762","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}
Yuanbing Wu, Ania Rashidpour, Wenwen Duan, Anna Fàbregas, María Pilar Almajano, Isidoro Metón
A single dose of chitosan-tripolyphosphate (TPP) nanoparticles carrying expression plasmids for fish codon-optimized Caenorhabditis elegans fat-1 and fat-2 was intraperitoneally administered to gilthead seabream (Sparus aurata) to stimulate the biosynthesis of omega-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFA) and evaluate subsequent short-term effects on liver intermediary metabolism and immunity. Seventy-two hours post-injection, the upregulation of fat-1 elevated eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total n-3 fatty acids in the liver, while fat-2 enhanced DHA and n-3 fatty acids. Co-expression of fat-1 and fat-2 increased EPA, DHA, PUFA, and the total n-6 and n-3 LC-PUFA, while reducing plasma triglycerides. The expression of fat-1 and fat-2 suppressed hepatic lipogenesis by downregulating srebf1 and pparg, and consequently key genes in fatty acid synthesis (acaca, acacb, fasn, scd1, and fads2). In contrast, the co-expression of fat-1 and fat-2 upregulated hnf4a, chrebp, and pfkl, a rate-limiting enzyme in glycolysis. Furthermore, fat-1 and fat-2 reduced hepatic proinflammatory markers such as tnfa and nfkb1. In addition to enhancing EPA and DHA biosynthesis, promoting glycolysis, and suppressing lipogenesis, our findings suggest that the short-term expression of C. elegans fat-1 and fat-2 in the liver may also reduce inflammation and, therefore, could impact the health and growth performance of cultured fish.
{"title":"Chitosan-Mediated Expression of <i>Caenorhabditis elegans fat-1</i> and <i>fat-2</i> in <i>Sparus aurata</i>: Short-Term Effects on the Hepatic Fatty Acid Profile, Intermediary Metabolism, and Proinflammatory Factors.","authors":"Yuanbing Wu, Ania Rashidpour, Wenwen Duan, Anna Fàbregas, María Pilar Almajano, Isidoro Metón","doi":"10.3390/md23110434","DOIUrl":"10.3390/md23110434","url":null,"abstract":"<p><p>A single dose of chitosan-tripolyphosphate (TPP) nanoparticles carrying expression plasmids for fish codon-optimized <i>Caenorhabditis elegans fat-1</i> and <i>fat-2</i> was intraperitoneally administered to gilthead seabream (<i>Sparus aurata</i>) to stimulate the biosynthesis of omega-3 long-chain polyunsaturated fatty acids (<i>n</i>-3 LC-PUFA) and evaluate subsequent short-term effects on liver intermediary metabolism and immunity. Seventy-two hours post-injection, the upregulation of <i>fat-1</i> elevated eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and total <i>n</i>-3 fatty acids in the liver, while <i>fat-2</i> enhanced DHA and <i>n</i>-3 fatty acids. Co-expression of <i>fat-1</i> and <i>fat-2</i> increased EPA, DHA, PUFA, and the total <i>n</i>-6 and <i>n</i>-3 LC-PUFA, while reducing plasma triglycerides. The expression of <i>fat-1</i> and <i>fat-2</i> suppressed hepatic lipogenesis by downregulating <i>srebf1</i> and <i>pparg</i>, and consequently key genes in fatty acid synthesis (<i>acaca</i>, <i>acacb</i>, <i>fasn</i>, <i>scd1</i>, and <i>fads2</i>). In contrast, the co-expression of <i>fat-1</i> and <i>fat-2</i> upregulated <i>hnf4a</i>, <i>chrebp</i>, and <i>pfkl</i>, a rate-limiting enzyme in glycolysis. Furthermore, <i>fat-1</i> and <i>fat-2</i> reduced hepatic proinflammatory markers such as <i>tnfa</i> and <i>nfkb1</i>. In addition to enhancing EPA and DHA biosynthesis, promoting glycolysis, and suppressing lipogenesis, our findings suggest that the short-term expression of <i>C. elegans fat-1</i> and <i>fat-2</i> in the liver may also reduce inflammation and, therefore, could impact the health and growth performance of cultured fish.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654412/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604617","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}
Elmira Khajavi Ahmadi, Said Al-Hamimi, Madeleine Jönsson, Roya R R Sardari
While numerous extraction methods have been applied to the brown algae Saccharina latissima, a systematic evaluation of how individual extraction parameters influence the extraction of each target polysaccharide has not previously been reported. Accordingly, this study compared conventional and advanced techniques for extracting fucoidan, laminarin, and alginate from pre-treated biomass. Conventional methods employed diluted acid (0.01 M and 0.1 M HCl), diluted alkali (0.01 M and 0.1 M NaOH), and hot water (121 °C for 30/60 min) for extraction. Advanced techniques involved pressurized liquid extraction (PLE) using water and moderate electric field (MEF) extraction with conditions optimized by statistical experimental design. Pre-treatment with aqueous ethanol removed 30% ash and eliminated mannitol, improving extraction selectivity. The results demonstrated fucoidan yields of 31% with 0.01 M HCl and 46% with 0.1 M NaOH, while 0.01 M NaOH facilitated laminarin co-extraction (45%). Alginate, as a mannuronic acid polymer, was obtained at 9% yield with 0.1 M HCl, 42% yield with 0.1 M NaOH, and 27% with pressurized hot water for 30 min. High-temperature, short-duration PLE further improved alginate yield, while MEF showed limited gains due to high ionic content but demonstrated potential under optimized settings. The results support a cascading biorefinery approach in which different polysaccharide fractions can be sequentially obtained, contributing to more sustainable seaweed valorization.
虽然褐藻Saccharina latisima的提取方法很多,但对于单个提取参数如何影响每种目标多糖的提取的系统评估尚未有报道。因此,本研究比较了从预处理生物质中提取岩藻聚糖、层藻素和海藻酸盐的传统和先进技术。传统的提取方法为稀酸(0.01 M和0.1 M HCl),稀碱(0.01 M和0.1 M NaOH),热水(121℃,30/60 min)。先进的技术包括水加压液体萃取(PLE)和适度电场萃取(MEF),并通过统计实验设计优化条件。水乙醇预处理去除30%灰分,去除甘露醇,提高萃取选择性。结果表明,在0.01 M HCl和0.1 M NaOH条件下,褐藻多糖的提取率分别为31%和46%,而在0.01 M NaOH条件下,层析蛋白的共萃取率为45%。海藻酸盐作为甘露醛酸聚合物,在0.1 M HCl条件下得率为9%,0.1 M NaOH条件下得率为42%,加压热水30 min得率为27%。高温、短时间PLE进一步提高了藻酸盐收率,而MEF由于离子含量高,收益有限,但在优化设置下显示出潜力。结果支持级联生物精炼方法,其中不同的多糖组分可以依次获得,有助于更可持续的海藻增值。
{"title":"Impact of Individual Process Parameters on Extraction of Polysaccharides from <i>Saccharina latissima</i>.","authors":"Elmira Khajavi Ahmadi, Said Al-Hamimi, Madeleine Jönsson, Roya R R Sardari","doi":"10.3390/md23110435","DOIUrl":"10.3390/md23110435","url":null,"abstract":"<p><p>While numerous extraction methods have been applied to the brown algae <i>Saccharina latissima</i>, a systematic evaluation of how individual extraction parameters influence the extraction of each target polysaccharide has not previously been reported. Accordingly, this study compared conventional and advanced techniques for extracting fucoidan, laminarin, and alginate from pre-treated biomass. Conventional methods employed diluted acid (0.01 M and 0.1 M HCl), diluted alkali (0.01 M and 0.1 M NaOH), and hot water (121 °C for 30/60 min) for extraction. Advanced techniques involved pressurized liquid extraction (PLE) using water and moderate electric field (MEF) extraction with conditions optimized by statistical experimental design. Pre-treatment with aqueous ethanol removed 30% ash and eliminated mannitol, improving extraction selectivity. The results demonstrated fucoidan yields of 31% with 0.01 M HCl and 46% with 0.1 M NaOH, while 0.01 M NaOH facilitated laminarin co-extraction (45%). Alginate, as a mannuronic acid polymer, was obtained at 9% yield with 0.1 M HCl, 42% yield with 0.1 M NaOH, and 27% with pressurized hot water for 30 min. High-temperature, short-duration PLE further improved alginate yield, while MEF showed limited gains due to high ionic content but demonstrated potential under optimized settings. The results support a cascading biorefinery approach in which different polysaccharide fractions can be sequentially obtained, contributing to more sustainable seaweed valorization.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604572","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}
The marine environment is a rich source of natural products that, as promising bioactive compounds, demonstrate environmentally friendly potential for application across various industries [...].
{"title":"Proteomic Studies for the Identification and Characterization of Marine Bioactive Molecules.","authors":"Nedeljka Rosic","doi":"10.3390/md23110433","DOIUrl":"10.3390/md23110433","url":null,"abstract":"<p><p>The marine environment is a rich source of natural products that, as promising bioactive compounds, demonstrate environmentally friendly potential for application across various industries [...].</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12653708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604846","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}
Sheyza Menéndez-Tasé, Evelin Gaeta-Leal, Darío Iker Téllez-Medina, Daniel Tapia-Maruri, Edgar Oliver López-Villegas, Georgina Calderón-Domínguez, Tzayhri Gallardo-Velázquez, Guillermo Osorio-Revilla, Mayuric Teresa Hernández-Botello, Diana Maylet Hernández-Martínez
The processing of fishery products generates a substantial amount of by-products, which can be utilized to promote a circular economy. The objective of the present study was to extract and characterize native collagen and total lipid extract from the fish skin and bones of crevalle jack (Caranx hippos). Physicochemical, structural, and morphological properties were evaluated for collagens. Chemical composition and functional properties were evaluated for lipid extracts. Native type I collagens were obtained by acid extraction, yielding approximately 2.64-6.16% (d.b.). The elemental chemical analysis showed its purity. The stability of the triple helix of collagen was verified through characteristic bands in the FTIR and UV spectra, the peaks at 2θ, around 7.5° and 19.5° obtained by XRD, and the bands of SDS-PAGE. Collagens show isoelectric points of 4.94 (skin) and 4.90 (bone), thermal stabilities of 53.40 °C (skin) and 46.88 °C (bone), and the percentage surface porosities of 41.28 (skin) and 38.84 (bone), all of which demonstrate their potential as a raw material in the biomedical field. The total lipids obtained were extracted using the Soxhlet and Folch methods. The extracts show EPA (1.26-3.16%) and DHA (3.94-9.78%) contents, with inhibition percentages of 32.7% (ABTS), 19.6% (DPPH), and 70.83% (β-carotene). These results highlight the potential of total lipid extract for nutraceutical and food applications.
{"title":"Native Collagen and Total Lipid Extract Obtained from <i>Caranx hyppos</i> By-Products: Characterization for Potential Use in the Biomedical and Nutraceutical Fields.","authors":"Sheyza Menéndez-Tasé, Evelin Gaeta-Leal, Darío Iker Téllez-Medina, Daniel Tapia-Maruri, Edgar Oliver López-Villegas, Georgina Calderón-Domínguez, Tzayhri Gallardo-Velázquez, Guillermo Osorio-Revilla, Mayuric Teresa Hernández-Botello, Diana Maylet Hernández-Martínez","doi":"10.3390/md23110432","DOIUrl":"10.3390/md23110432","url":null,"abstract":"<p><p>The processing of fishery products generates a substantial amount of by-products, which can be utilized to promote a circular economy. The objective of the present study was to extract and characterize native collagen and total lipid extract from the fish skin and bones of crevalle jack (<i>Caranx hippos</i>). Physicochemical, structural, and morphological properties were evaluated for collagens. Chemical composition and functional properties were evaluated for lipid extracts. Native type I collagens were obtained by acid extraction, yielding approximately 2.64-6.16% (d.b.). The elemental chemical analysis showed its purity. The stability of the triple helix of collagen was verified through characteristic bands in the FTIR and UV spectra, the peaks at 2θ, around 7.5° and 19.5° obtained by XRD, and the bands of SDS-PAGE. Collagens show isoelectric points of 4.94 (skin) and 4.90 (bone), thermal stabilities of 53.40 °C (skin) and 46.88 °C (bone), and the percentage surface porosities of 41.28 (skin) and 38.84 (bone), all of which demonstrate their potential as a raw material in the biomedical field. The total lipids obtained were extracted using the Soxhlet and Folch methods. The extracts show EPA (1.26-3.16%) and DHA (3.94-9.78%) contents, with inhibition percentages of 32.7% (ABTS), 19.6% (DPPH), and 70.83% (β-carotene). These results highlight the potential of total lipid extract for nutraceutical and food applications.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604662","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}
Diaa T A Youssef, Areej S Alqarni, Lamiaa A Shaala, Alaa A Bagalagel, Sana A Fadil, Abdelsattar M Omar, Mostafa E Rateb
Marine-derived species of the genus Alternaria are widely distributed across diverse aquatic habitats, functioning as pathogens, endophytes, and saprophytes. These fungi are notable for their ability to produce structurally diverse secondary metabolites with potent bioactivities. Between 2003 and 2023, a total of 67 marine-derived Alternaria species were reported and investigated, collectively yielding 319 compounds. Most of these fungal isolates were from Chinese marine territories (53 species; ~79%), followed by isolates from Korea, Japan, India, Egypt, Saudi Arabia, and oceanic regions such as the Atlantic and Pacific. The fungal isolates were mainly obtained from marine plants (26 isolates) and marine animals (23 isolates), with additional sources including sediments (13) and seawater (3). Among the metabolites investigated in different screens, approximately 56% demonstrated measurable bioactivities, with anti-inflammatory (51 active compounds), antimicrobial (41 compounds), cytotoxic (39 compounds), and phytotoxic (52 compounds) activities being the most frequently reported. Additionally, compounds with antiparasitic, antidiabetic and antioxidant effects are reported. The chemical diversity of Alernaria-derived compounds spans multiple structural groups, including nitrogenous compounds, steroids, terpenoids, pyranones, quinones, and phenolics. Notably, compounds such as alternariol, alternariol monomethyl ether, and alternariol-9-methyl ether exhibit broad pharmacological potential, including antibacterial, antifungal, antiviral, immunomodulatory, and anticancer effects. Several metabolites also modulate cytokine production (e.g., IL-10, TNF-α), underscoring their relevance as immunomodulatory agents. Taken together, marine-derived Alternaria compounds represent a prolific and underexplored source of structurally and biologically diverse secondary metabolites with potential applications in drug discovery, agriculture, and biotechnology. This review provides an updated and comprehensive overview of the chemical and biological diversity of Alternaria metabolites reported over the past two decades, emphasizing their biomedical relevance and potential to inspire further research into their ecological functions, biosynthetic mechanisms, and industrial applications.
{"title":"Two Decades of Research on Marine-Derived <i>Alternaria</i>: Structural Diversity, Biomedical Potential, and Applications.","authors":"Diaa T A Youssef, Areej S Alqarni, Lamiaa A Shaala, Alaa A Bagalagel, Sana A Fadil, Abdelsattar M Omar, Mostafa E Rateb","doi":"10.3390/md23110431","DOIUrl":"10.3390/md23110431","url":null,"abstract":"<p><p>Marine-derived species of the genus <i>Alternaria</i> are widely distributed across diverse aquatic habitats, functioning as pathogens, endophytes, and saprophytes. These fungi are notable for their ability to produce structurally diverse secondary metabolites with potent bioactivities. Between 2003 and 2023, a total of 67 marine-derived <i>Alternaria</i> species were reported and investigated, collectively yielding 319 compounds. Most of these fungal isolates were from Chinese marine territories (53 species; ~79%), followed by isolates from Korea, Japan, India, Egypt, Saudi Arabia, and oceanic regions such as the Atlantic and Pacific. The fungal isolates were mainly obtained from marine plants (26 isolates) and marine animals (23 isolates), with additional sources including sediments (13) and seawater (3). Among the metabolites investigated in different screens, approximately 56% demonstrated measurable bioactivities, with anti-inflammatory (51 active compounds), antimicrobial (41 compounds), cytotoxic (39 compounds), and phytotoxic (52 compounds) activities being the most frequently reported. Additionally, compounds with antiparasitic, antidiabetic and antioxidant effects are reported. The chemical diversity of <i>Alernaria</i>-derived compounds spans multiple structural groups, including nitrogenous compounds, steroids, terpenoids, pyranones, quinones, and phenolics. Notably, compounds such as alternariol, alternariol monomethyl ether, and alternariol-9-methyl ether exhibit broad pharmacological potential, including antibacterial, antifungal, antiviral, immunomodulatory, and anticancer effects. Several metabolites also modulate cytokine production (e.g., IL-10, TNF-α), underscoring their relevance as immunomodulatory agents. Taken together, marine-derived <i>Alternaria</i> compounds represent a prolific and underexplored source of structurally and biologically diverse secondary metabolites with potential applications in drug discovery, agriculture, and biotechnology. This review provides an updated and comprehensive overview of the chemical and biological diversity of <i>Alternaria</i> metabolites reported over the past two decades, emphasizing their biomedical relevance and potential to inspire further research into their ecological functions, biosynthetic mechanisms, and industrial applications.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604787","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}
Ester Colarusso, Assunta Giordano, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro
Marine ecosystems represent an exceptional reservoir of structurally diverse metabolites with remarkable pharmacological potential. Over the past decades, the exploration of marine organisms has led to the discovery of an ever-expanding number of bioactive compounds. Many of these metabolites display highly original chemical scaffolds that are not typically found in terrestrial organisms, offering new opportunities for drug discovery. Among the most promising applications is their development as anticancer agents, given their ability to interfere with key cellular processes. This review highlights marine natural products currently under investigation in preclinical studies as potential anticancer lead compounds. The molecules are classified into major structural families: aromatic and heterocyclic alkaloids, terpenes and their derivatives, macrolide frameworks, and diverse peptide-based scaffolds, alongside other complex classes (polyketides, thiazole lipids, alkylamino alcohols, and pyrrolocarbazole derivatives). A particular emphasis has been placed on the role of total synthesis over the last decade. Advances in synthetic methodology have not only enabled the production of these complex metabolites in sufficient quantities but have also facilitated the development of novel chemotherapeutic agents. To overcome the challenges of limited natural availability, the advanced synthetic approaches are crucial for harnessing the full therapeutic potential of marine-derived compounds.
{"title":"Marine Natural Products in Preclinical Cancer Studies: Ten Years of Advanced Total Synthesis.","authors":"Ester Colarusso, Assunta Giordano, Maria Giovanna Chini, Giuseppe Bifulco, Gianluigi Lauro","doi":"10.3390/md23110430","DOIUrl":"10.3390/md23110430","url":null,"abstract":"<p><p>Marine ecosystems represent an exceptional reservoir of structurally diverse metabolites with remarkable pharmacological potential. Over the past decades, the exploration of marine organisms has led to the discovery of an ever-expanding number of bioactive compounds. Many of these metabolites display highly original chemical scaffolds that are not typically found in terrestrial organisms, offering new opportunities for drug discovery. Among the most promising applications is their development as anticancer agents, given their ability to interfere with key cellular processes. This review highlights marine natural products currently under investigation in preclinical studies as potential anticancer lead compounds. The molecules are classified into major structural families: aromatic and heterocyclic alkaloids, terpenes and their derivatives, macrolide frameworks, and diverse peptide-based scaffolds, alongside other complex classes (polyketides, thiazole lipids, alkylamino alcohols, and pyrrolocarbazole derivatives). A particular emphasis has been placed on the role of total synthesis over the last decade. Advances in synthetic methodology have not only enabled the production of these complex metabolites in sufficient quantities but have also facilitated the development of novel chemotherapeutic agents. To overcome the challenges of limited natural availability, the advanced synthetic approaches are crucial for harnessing the full therapeutic potential of marine-derived compounds.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654674/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604683","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}
Two new chromone derivatives, cnidimols I and J (1 and 2), together with ten known aromatic derivatives (3-12), were isolated from the Beibu Gulf algicolous fungus Aspergillus versicolor GXIMD 02518. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations of 1 and 2 were accomplished by ECD calculations and X-ray diffraction analysis. Compound 1 was obtained as a pair of enantiomers, which were separated by chiral-phase HPLC analysis. Notably, 3,7-dihydroxy-1,9-dimethyldibenzofuran (6) displayed significant inhibition in LPS-induced NF-κB luciferase activity in RAW 264.7 macrophages, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophage cells.
{"title":"Two New Chromone Derivatives from a Marine Algicolous Fungus <i>Aspergillus versicolor</i> GXIMD 02518 and Their Osteoclastogenesis Inhibitory Activity.","authors":"Xin Qi, Zhen Li, Miaoping Lin, Humu Lu, Shuai Peng, Huangxue Qin, Yonghong Liu, Chenghai Gao, Xiaowei Luo","doi":"10.3390/md23110429","DOIUrl":"10.3390/md23110429","url":null,"abstract":"<p><p>Two new chromone derivatives, cnidimols I and J (<b>1</b> and <b>2</b>), together with ten known aromatic derivatives (<b>3</b>-<b>12</b>), were isolated from the Beibu Gulf algicolous fungus <i>Aspergillus versicolor</i> GXIMD 02518. Their structures were determined by comprehensive physicochemical and spectroscopic data interpretation. The absolute configurations of <b>1</b> and <b>2</b> were accomplished by ECD calculations and X-ray diffraction analysis. Compound <b>1</b> was obtained as a pair of enantiomers, which were separated by chiral-phase HPLC analysis. Notably, 3,7-dihydroxy-1,9-dimethyldibenzofuran (<b>6</b>) displayed significant inhibition in LPS-induced NF-κB luciferase activity in RAW 264.7 macrophages, which further inhibited RANKL-induced osteoclast differentiation without cytotoxicity in bone marrow macrophage cells.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12653716/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604814","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}
Daniil V Mosievich, Nadezhda G Balabushevich, Pavel I Mishin, Lyubov Y Filatova, Marina A Murina, Olga V Pobeguts, Maria A Galyamina, Ekaterina A Obraztsova, Daria V Grigorieva, Irina V Gorudko, Alexey V Sokolov, Ekaterina V Shmeleva, Oleg M Panasenko, Elena V Mikhalchik
Fucoidan is of considerable interest for the development of drug carriers. The inclusion of fucoidan allows calcium carbonate microparticles in the form of vaterite to acquire new properties, enabling their use in the immobilization of protein preparations. In this work, we investigated the properties of hybrid vaterite microparticles with fucoidan from Fucus vesiculosus obtained by co-precipitation and loaded with recombinant human lactoferrin from goats. The hybrid microparticles had a smaller diameter (3-4 µm), larger surface area (35-36 m2g-1), smaller pore size (5-10 nm average), and more negative ζ-potential (-(11-13) mV) than the control vaterite microparticles. The incorporation of lactoferrin into the microparticles by co-precipitation in complex with fucoidan was greater than when the protein was adsorbed onto the hybrid microparticles. Microparticles with fucoidan and lactoferrin were stable in acidic environments, released both components over a prolonged period at pH 7.4, and possessed mucoadhesive properties and anticoagulant activity. The antibacterial properties of hybrid microparticles with fucoidan and lactoferrin against Bacillus subtilis were characterized. Microparticles of vaterite with fucoidan can serve as a platform for the microfabrication of effective means of delivering therapeutic proteins.
{"title":"Vaterite/Fucoidan Hybrid Microparticles: Fabrication, Loading of Lactoferrin, Structural Characteristics and Functional Properties.","authors":"Daniil V Mosievich, Nadezhda G Balabushevich, Pavel I Mishin, Lyubov Y Filatova, Marina A Murina, Olga V Pobeguts, Maria A Galyamina, Ekaterina A Obraztsova, Daria V Grigorieva, Irina V Gorudko, Alexey V Sokolov, Ekaterina V Shmeleva, Oleg M Panasenko, Elena V Mikhalchik","doi":"10.3390/md23110428","DOIUrl":"10.3390/md23110428","url":null,"abstract":"<p><p>Fucoidan is of considerable interest for the development of drug carriers. The inclusion of fucoidan allows calcium carbonate microparticles in the form of vaterite to acquire new properties, enabling their use in the immobilization of protein preparations. In this work, we investigated the properties of hybrid vaterite microparticles with fucoidan from <i>Fucus vesiculosus</i> obtained by co-precipitation and loaded with recombinant human lactoferrin from goats. The hybrid microparticles had a smaller diameter (3-4 µm), larger surface area (35-36 m<sup>2</sup>g<sup>-1</sup>), smaller pore size (5-10 nm average), and more negative ζ-potential (-(11-13) mV) than the control vaterite microparticles. The incorporation of lactoferrin into the microparticles by co-precipitation in complex with fucoidan was greater than when the protein was adsorbed onto the hybrid microparticles. Microparticles with fucoidan and lactoferrin were stable in acidic environments, released both components over a prolonged period at pH 7.4, and possessed mucoadhesive properties and anticoagulant activity. The antibacterial properties of hybrid microparticles with fucoidan and lactoferrin against <i>Bacillus subtilis</i> were characterized. Microparticles of vaterite with fucoidan can serve as a platform for the microfabrication of effective means of delivering therapeutic proteins.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12653817/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604844","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}
Blanca Del Sol Villalba-Urquidy, Wilfrido Torres-Arreola, Isabel Medina, Laura Estefany Hernández-Aguirre, Jesús Enrique Chan-Higuera, Josafat Marina Ezquerra-Brauer
Jellyfish, a promising source of bioactive compounds, has attracted the attention of the biotechnology sector. This research explored the antioxidant and antimutagenic properties and the genotoxicity of peptides derived from blue cannonball jellyfish (Stomolophus sp. 2) collagen hydrolysates (JCH) as potential food supplements. Firstly, JCH was fractionated into three parts based on molecular weight. Notably, the low-molecular-weight hydrolyzed fraction (<3 kDa) exhibited the highest bioactivity, with ABTS scavenging activity of 8993 ± 5.2 μmol TE/g and an antimutagenic inhibition rate against AFB1 of 88%. This fraction remained non-genotoxic at 100 ppm, suggesting its suitability for potential applications without evidence of genotoxic damage. In addition, in silico analysis revealed 15 unique peptides in Stomolophus sp. 2 collagen hydrolysates, ten of which showed particularly promising bioactive potential. Peptides from Stomolophus sp. 2 with molecular weights under 3 kDa exhibit remarkable bioactivity and hold great promise for future research on molecular characterization and bioactive food supplements.
{"title":"Bioactivity and in Silico Insights of Collagen-Derived Peptides from Jellyfish (<i>Stomolophus</i> sp. 2) Mesoglea.","authors":"Blanca Del Sol Villalba-Urquidy, Wilfrido Torres-Arreola, Isabel Medina, Laura Estefany Hernández-Aguirre, Jesús Enrique Chan-Higuera, Josafat Marina Ezquerra-Brauer","doi":"10.3390/md23110427","DOIUrl":"10.3390/md23110427","url":null,"abstract":"<p><p>Jellyfish, a promising source of bioactive compounds, has attracted the attention of the biotechnology sector. This research explored the antioxidant and antimutagenic properties and the genotoxicity of peptides derived from blue cannonball jellyfish (<i>Stomolophus</i> sp. 2) collagen hydrolysates (JCH) as potential food supplements. Firstly, JCH was fractionated into three parts based on molecular weight. Notably, the low-molecular-weight hydrolyzed fraction (<3 kDa) exhibited the highest bioactivity, with ABTS scavenging activity of 8993 ± 5.2 μmol TE/g and an antimutagenic inhibition rate against AFB<sub>1</sub> of 88%. This fraction remained non-genotoxic at 100 ppm, suggesting its suitability for potential applications without evidence of genotoxic damage. In addition, in silico analysis revealed 15 unique peptides in <i>Stomolophus</i> sp. 2 collagen hydrolysates, ten of which showed particularly promising bioactive potential. Peptides from <i>Stomolophus</i> sp. 2 with molecular weights under 3 kDa exhibit remarkable bioactivity and hold great promise for future research on molecular characterization and bioactive food supplements.</p>","PeriodicalId":18222,"journal":{"name":"Marine Drugs","volume":"23 11","pages":""},"PeriodicalIF":5.4,"publicationDate":"2025-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12654391/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145604365","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}