Journal Description
Marine Drugs
Marine Drugs
is an international, peer-reviewed, open access journal on the research, development, and production of biologically and therapeutically active compounds from the sea, published monthly online by MDPI. The Australia New Zealand Marine Biotechnology Society (ANZMBS) is affiliated with Marine Drugs and its members receive discounts on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, MEDLINE, PMC, Embase, PubAg, MarinLit, AGRIS, and other databases.
- Journal Rank: JCR - Q1 (Pharmacology and Pharmacy) / CiteScore - Q1 (Pharmacology, Toxicology and Pharmaceutics (miscellaneous))
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 13.6 days after submission; acceptance to publication is undertaken in 1.9 days (median values for papers published in this journal in the second half of 2025).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Journal Clusters-Pharmaceutical Science: Scientia Pharmaceutica, Marine Drugs, Pharmaceuticals, Pharmaceutics, Pharmacy, Future Pharmacology, Pharmacoepidemiology, Drugs and Drug Candidates and Journal of Pharmaceutical and BioTech Industry.
Impact Factor:
5.4 (2024);
5-Year Impact Factor:
5.6 (2024)
Latest Articles
From Host-Derived Pressures to the Environmental Anti-Antimicrobial Peptides Resistome: Mechanisms, Reservoirs and Implications for Therapeutic Peptide Design
Mar. Drugs 2026, 24(2), 76; https://doi.org/10.3390/md24020076 (registering DOI) - 12 Feb 2026
Abstract
Antimicrobial peptides (AMPs) are increasingly promoted as alternatives or complements to conventional antibiotics, yet growing evidence demonstrates that resistance to AMPs is neither rare nor incidental. Here, we define the anti-AMP resistome as a coordinated network of genetic, regulatory, and physiological mechanisms that
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Antimicrobial peptides (AMPs) are increasingly promoted as alternatives or complements to conventional antibiotics, yet growing evidence demonstrates that resistance to AMPs is neither rare nor incidental. Here, we define the anti-AMP resistome as a coordinated network of genetic, regulatory, and physiological mechanisms that enable bacteria to tolerate or evade AMP-mediated stress. We synthesize advances in understanding how envelope remodeling, efflux and sequestration, extracellular proteolysis, biofilm-associated buffering, and inducible stress responses collectively shape AMP susceptibility. We further distinguish transient, inducible tolerance from stable, heritable resistance, and discuss how chronic subinhibitory exposure can drive their evolutionary interconversion. Extending beyond clinical pathogens, we highlight environmental microbiomes as major reservoirs of anti-AMP determinants with implications for horizontal transfer and One Health risk. Finally, we argue that AMP development and deployment must adopt a resistome-aware framework that integrates molecular mechanisms, evolutionary dynamics, and environmental context to preserve long-term therapeutic efficacy.
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(This article belongs to the Section Marine Pharmacology)
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Open AccessArticle
Anticancer Effect of Pacificusoside D from the Starfish Solaster pacificus in Combination with 2-Deoxy-D-glucose on Oxidative Phosphorylation in Triple-Negative Breast Cancer Cells MDA-MB-231
by
Olesya S. Malyarenko, Timofey V. Malyarenko, Alla A. Kicha, Svetlana P. Ermakova and Natalia V. Ivanchina
Mar. Drugs 2026, 24(2), 75; https://doi.org/10.3390/md24020075 (registering DOI) - 11 Feb 2026
Abstract
Triple-negative breast cancer (TNBC) represents significant therapeutic challenges due to its aggressive behavior, metabolic plasticity, and lack of targeted treatments, prompting investigation of biologically active triterpene glycosides from the starfish Solaster pacificus. This study evaluated the ability of pacificusoside D (SpD) to
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Triple-negative breast cancer (TNBC) represents significant therapeutic challenges due to its aggressive behavior, metabolic plasticity, and lack of targeted treatments, prompting investigation of biologically active triterpene glycosides from the starfish Solaster pacificus. This study evaluated the ability of pacificusoside D (SpD) to synergistically enhance the anticancer efficacy of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) in TNBC MDA-MB-231 cells by targeting mitochondrial oxidative phosphorylation (OXPHOS). Methods included metabolic profiling via glucose uptake, lactate, and glutamate Glo assays; IC50 determination by MTS and trypan blue assays; colony formation evaluation using a soft agar assay; and molecular mechanism elucidation by Western blot, fluorescence microscopy and spectrometry, and flow cytometry analyses. Results demonstrated that MDA-MB-231 cells predominantly utilized glycolysis under basal conditions, shifting to OXPHOS with 2-DG (0.5 mM). IC50 values were 8.0/8.4 mM for 2-DG and 0.3/0.25 μM for SpD after 24 h of cell treatment. SpD exhibited a significant decrease in the number of colonies in MDA-MB-231 cells and possessed synergistic anticancer effects with 2-DG. Mechanistically, SpD increased tumor suppressor VHL expression level, down-regulated expression level of electron transport chain enzymes, generated reactive oxygen species, induced mitochondrial dysfunction, and triggered Bax/Bak-mediated apoptosis. These findings highlighted the synergistic anticancer potential of SpD in combination with 2-DG in aggressive breast cancer, offering insights into improved clinical outcomes in the future.
Full article
(This article belongs to the Special Issue Marine Natural Products as Anticancer Agents, 5th Edition)
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Open AccessReview
Shellfish as a Source of Bioactive Compounds and Extracts: A Comprehensive Review of Their Anticancer and Antimicrobial Properties
by
N. M. Liyanage, Li Yiqiao, K. K. Asanka Sanjeewa, Kyung Yuk Ko, D. P. Nagahawatta and You-Jin Jeon
Mar. Drugs 2026, 24(2), 74; https://doi.org/10.3390/md24020074 - 11 Feb 2026
Abstract
Shellfish are a diverse group of marine animals that play a significant role, as a high proportion of the world’s seafood is produced by shellfish. In general, shellfish contain higher amounts of nutrients that benefit consumer health. In recent years, research has focused
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Shellfish are a diverse group of marine animals that play a significant role, as a high proportion of the world’s seafood is produced by shellfish. In general, shellfish contain higher amounts of nutrients that benefit consumer health. In recent years, research has focused on the potential health benefits of consuming shellfish, including their anti-cancer and anti-microbial properties. Studies have shown that certain types of shellfish contain bioactive compounds that can inhibit growth and proliferation as well as induce apoptosis in cancer cells both in vitro and in vivo. In addition, shellfish also possess anti-microbial properties which arise from their proteins, peptides, fatty acids, and polysaccharides, which can disrupt the bacterial cell membrane, inhibit bacterial cell division, and interfere with cellular processes. These make them beneficial in preventing and treating infectious diseases. This review explored the findings related to the potential of shellfish bioactive compounds against cancer and microbial infections. Furthermore, this analysis demonstrates unequivocally that shellfish have vast potential for producing functional foods and that the bioactive compounds have the potential to be used in pharmaceutical applications.
Full article
(This article belongs to the Special Issue Biologically Active Compounds from Marine Invertebrates 2025)
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Open AccessEditorial
Commemorating the Launch of the Section “Marine Toxins”
by
Andrew Turner and Panagiota Katikou
Mar. Drugs 2026, 24(2), 73; https://doi.org/10.3390/md24020073 - 10 Feb 2026
Abstract
Marine toxins are natural compounds produced by a variety of marine organisms, including microalgae, bacteria, and macroalgae [...]
Full article
(This article belongs to the Special Issue Commemorating the Launch of the Section "Marine Toxins")
Open AccessArticle
Sulfated Pelvetia siliquosa Polysaccharides Attenuate Pyroptosis via NF-κB Pathway Inhibition Against Calcium Oxalate Stone Formation
by
Xin-Yi Tong, Xue-Wu Chen, Jia-Yi Zhang and Jian-Ming Ouyang
Mar. Drugs 2026, 24(2), 72; https://doi.org/10.3390/md24020072 - 8 Feb 2026
Abstract
Objective: The formation of calcium oxalate (CaOx) kidney stones is accompanied by the pyroptosis of renal epithelial cells. The risk of kidney stone formation can possibly be reduced through pyroptosis inhibition. Methods: Pyroptosis of HK-2 cells induced by 3 µm CaOx monohydrate (COM-3
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Objective: The formation of calcium oxalate (CaOx) kidney stones is accompanied by the pyroptosis of renal epithelial cells. The risk of kidney stone formation can possibly be reduced through pyroptosis inhibition. Methods: Pyroptosis of HK-2 cells induced by 3 µm CaOx monohydrate (COM-3 µm) was inhibited by Pelvetia siliquosa polysaccharides before and after sulfation (PSP0 and PSP3, with −OSO3− contents of 1.04% and 36.12%, respectively). The inhibitory efficiency and mechanism of PSP0 and PSP3 were evaluated via caspase-1/PI double staining and Western blot detection of pathway proteins in pyroptosis cells. The potential anti-stone effect of polysaccharides was evaluated through measurement of the extent of crystal adhesion on the cell surface. Results: The proportion of pyroptosis cells induced by COM-3 µm reached 17.87%. After protection by PSP0 and PSP3, the percentage of pyroptosis cells was reduced to 12.7% and 6.35%. The levels of NLRP3, ASC, gasdermin D, IL-1β, and IL-18 related to pyroptosis were downregulated. In addition, the activation of the NF-κB pathway was considerably inhibited. During inhibition of pyroptosis, reactive oxygen species and lactate dehydrogenase levels were decreased, the integrity of zonula occludens-1 protein was restored, and the expressions of CaOx-specific adhesion proteins (ANXA3 and CD44) were substantially decreased. As a result, the adhesion of COM crystals on the cell surface was reduced. PSP3 exhibited a higher protection energy efficiency than PSP0. Conclusions: PSP0 and PSP3 inhibited the pyroptosis of HK-2 cells through the NLRP3/ASC/caspase-1/IL-1β pathway, which caused the inhibition of cell inflammation and injury, reduced the expressions of adhesion proteins, and reduced the risk of CaOx crystal adhesion and stone formation. The biological activity of PSP0 and PSP3 after sulfation modification increased.
Full article
(This article belongs to the Special Issue Marine Sulfated Polysaccharides and Their Biomedical Applications)
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Open AccessReview
Marine Algae-Derived Bioactive Compounds Stabilizing Collagen-Rich Dental Matrices Through Matrix Metalloproteinase Inhibition: A Scoping Review
by
Won Sek Lee, Sung-Ae Son and Yong-Il Kim
Mar. Drugs 2026, 24(2), 71; https://doi.org/10.3390/md24020071 - 8 Feb 2026
Abstract
This scoping review mapped the available evidence on marine algae-derived bioactive compounds, focusing on their biological activities related to collagen stabilization, matrix metalloproteinase (MMP) inhibition, and enamel remineralization in dental hard tissues. Four electronic databases (PubMed, Scopus, Embase, and Web of Science) were
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This scoping review mapped the available evidence on marine algae-derived bioactive compounds, focusing on their biological activities related to collagen stabilization, matrix metalloproteinase (MMP) inhibition, and enamel remineralization in dental hard tissues. Four electronic databases (PubMed, Scopus, Embase, and Web of Science) were systematically searched following a predefined protocol. Original experimental studies involving human or animal dental hard tissues were included. Nine studies met the inclusion criteria. Brown algal derivatives, including fucoxanthin, fucosterol, and phloroglucinol, exhibited significant MMP inhibition and, in selected compounds, collagen cross-linking, contributing to enhanced mechanical properties and improved stability of collagen-rich matrices. In contrast, red algae extracts such as Lithothamnion calcareum primarily promoted enamel remineralization, achieving surface microhardness recovery comparable to or superior to 0.05% sodium fluoride. Alginate, a brown algae-derived polysaccharide, also demonstrated functional potential as a scaffold biomaterial through strong hydroxyapatite adsorption and suitability for three-dimensional scaffold fabrication. Overall, marine algae-derived compounds demonstrate biologically relevant activities that modulate collagen stability, enzymatic function, and mineral deposition processes. These findings highlight the pharmacological potential of marine bioactive compounds, with dental hard tissues representing a primary application context. However, further validation using clinically relevant models is required.
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(This article belongs to the Section Biomaterials of Marine Origin)
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Open AccessReview
Marine-Derived Defenses Against HIV: Emerging Bioactive Molecules from the Seas
by
Tiago Santos, Ana Pintão, Carolina S. Marques and Pedro Brandão
Mar. Drugs 2026, 24(2), 70; https://doi.org/10.3390/md24020070 - 7 Feb 2026
Abstract
Marine ecosystems have yielded a remarkable diversity of bioactive metabolites with relevance for antiviral drug discovery. This article reviews recent advances in marine-derived compounds investigated as anti-HIV agents. Metabolites, such as sulfated polysaccharides, lectins, alkaloids, and terpenoids, display inhibitory activity across multiple stages
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Marine ecosystems have yielded a remarkable diversity of bioactive metabolites with relevance for antiviral drug discovery. This article reviews recent advances in marine-derived compounds investigated as anti-HIV agents. Metabolites, such as sulfated polysaccharides, lectins, alkaloids, and terpenoids, display inhibitory activity across multiple stages of the HIV life cycle, including viral entry, reverse transcription, integration, and maturation. From sponge-inspired development of AZT to the application of Griffithin in clinical trials for the prophylaxis of the HIV infection, recent discoveries showcase the chemical diversity of marine ecosystems and validate their utility as hit and compound sources in drug discovery. We highlight possible mechanisms of action, as well as translational hurdles from research to clinical trials. Overall, marine biodiversity represents a valuable and underexploited reservoir for the development of novel HIV therapeutics.
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(This article belongs to the Section Marine Pharmacology)
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Open AccessArticle
Anti-Inflammatory Effects of Marine-Derived Resorcylic Acid Lactone Derivatives in Ulcerative Colitis via the MAPK/ERK Pathway
by
Xuan Zhang, Tuxiang Mo, Yuyue Qin, Meiling Le, Li Tang, Zhao Zhang, Jiling Yi, Fuling Cen, Wanshan Li and Guangying Chen
Mar. Drugs 2026, 24(2), 69; https://doi.org/10.3390/md24020069 - 5 Feb 2026
Abstract
Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammation of the colonic mucosa, and there is currently a lack of safe and effective treatment drugs. Resorcylic acid lactones (RALs) are a natural product that have been reported to have anti-inflammatory
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Ulcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent inflammation of the colonic mucosa, and there is currently a lack of safe and effective treatment drugs. Resorcylic acid lactones (RALs) are a natural product that have been reported to have anti-inflammatory effects. However, the mechanism of whether RALs can treat UC and their anti-inflammatory effects remains underexplored. In this study, three new RAL derivatives, Penicillactones A–C (1–3), along with seven known analogs (4–10), were isolated from the marine fungus Penicillium sp. HN20. The structures of compounds 1–3 were elucidated by spectroscopic methods, 13C NMR theoretical calculations, and ECD analysis. Among these, compound 4 exhibited potent anti-inflammatory activity in LPS-stimulated RAW 264.7 macrophages. In a dextran sulfate sodium (DSS)-induced UC model, compound 4 alleviated body weight loss, disease activity, colon shortening, and spleen enlargement, and protected intestinal epithelial integrity. Mechanistic studies revealed that compound 4 primarily exerts its effects by downregulating the Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase (MAPK/ERK) signaling pathway, inhibiting pro-inflammatory cytokine production. Collectively, these findings provide the first evidence that marine-derived RAL derivatives exert anti-inflammatory effects by inhibiting the MAPK/ERK pathway, highlighting compound 4 as a promising therapeutic candidate for inflammation and UC.
Full article
(This article belongs to the Special Issue Pharmacological Potential of Marine Natural Products, 3rd Edition)
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Open AccessArticle
Taxonomic Diversity and Metabolic and Pharmacological Profiles of Marine-Derived Actinomycetes from the Lisbon and Setúbal Coast, Portugal
by
Miguel P. Coelho, Pablo Suárez-Moo, Mariana Rocha, Artur O. G. Matos, Vanda Marques, Sara Margarida, Mário Mil-Homens, Alejandra Prieto-Davó, Cecília M. P. Rodrigues, Anelize Bauermeister, Rita G. Sobral and Susana P. Gaudêncio
Mar. Drugs 2026, 24(2), 68; https://doi.org/10.3390/md24020068 - 3 Feb 2026
Abstract
This study explores the taxonomic diversity, metabolic profile, and bioactivity of marine-derived actinomycetes isolated from sediments collected off the coast of Lisbon and Setúbal Peninsula, Portugal. The combined use of two sediment pre-treatments (heat shock and dry overnight) and four growth media with
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This study explores the taxonomic diversity, metabolic profile, and bioactivity of marine-derived actinomycetes isolated from sediments collected off the coast of Lisbon and Setúbal Peninsula, Portugal. The combined use of two sediment pre-treatments (heat shock and dry overnight) and four growth media with varying nutrient concentrations revealed that formulations 10% A1 and SWA were most effective for recovering diverse actinomycetes, including rare Actinomadura, resulting in a total of 142 cultivable strains closely related to 47 phylogenetic distinct species dominated by Streptomyces and Micromonospora. Antimicrobial screening against methicillin-resistant Staphylococcus aureus (MRSA, COL) and Escherichia coli (K12) identified 22 bioactive strains, with strain PTS-083 exhibiting the strongest activity against MRSA (MIC = 1.95 µg/mL) and a 98.30% 16S rRNA gene identity to S. chumphonensis, highlighting it as a strong candidate for further metabolite and genomic studies. Cytotoxicity assays against HCT-116 human colorectal adenocarcinoma cells revealed eight bioactive strains with potent anticancer activity for extracts from strains related to S. sundarbansensis, S. violaceorubidus, and S. aculeolatus (IC50 < 0.005–5.08 µg/mL). Untargeted LC-MS/MS metabolomic analysis uncovered a wide array of secondary metabolites, including macrolides, siderophores, fatty acids, and cyclic peptides. Comparative analyses with other Portuguese coastal studies revealed both shared and distinctive metabolomic profiles, emphasizing the importance of exhaustive sampling, even at nearby locations, since localized environmental conditions can influence metabolic diversity and are crucial for uncovering unique metabolites with potential biotechnological value. These findings highlight Portugal’s coastal sediments as a rich and underexplored source of novel actinomycetes and bioactive compounds with promising pharmaceutical applications.
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(This article belongs to the Section Marine Pharmacology)
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Open AccessArticle
Brevetoxin Metabolites: Emerging Toxins in French Shellfish Determined by LC-MS/MS and ELISA
by
Zouher Amzil, Amélie Derrien, Korian Lhaute, Aouregan Terre Terrillon and Simon Tanniou
Mar. Drugs 2026, 24(2), 67; https://doi.org/10.3390/md24020067 - 3 Feb 2026
Abstract
In France, as part of the monitoring program for the emergence of marine toxins in shellfish (EMERGTOX), brevetoxins (BTX-2, BTX-3) were first detected in shellfish from Corsica (Mediterranean Sea) in 2018. The complex metabolic transformation of brevetoxins in shellfish, coupled with the limited
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In France, as part of the monitoring program for the emergence of marine toxins in shellfish (EMERGTOX), brevetoxins (BTX-2, BTX-3) were first detected in shellfish from Corsica (Mediterranean Sea) in 2018. The complex metabolic transformation of brevetoxins in shellfish, coupled with the limited availability of analytical standards for most metabolites, complicates the accurate evaluation of contamination levels. To address this challenge, two complementary analytical approaches were implemented to quantify brevetoxin metabolites in shellfish samples collected from 2018 to 2023: (i) a targeted LC-MS/MS method specially developed for brevetoxins; and (ii) an ELISA capable of detecting metabolites for which no reference standards are available. Of the 11 brevetoxin metabolites targeted, 4 were quantified by LC-MS/MS: BTX-2, BTX-3, BTX-B5, and S-deoxy-BTX-B2 (including its isomers). The ELISA consistently detected brevetoxins in all Corsican samples previously confirmed positive by LC-MS/MS, with concentrations systematically exceeding those measured by LC-MS/MS. This overestimation may result from antibody cross-reactivity and from the presence of unidentified brevetoxin metabolites not detected by LC-MS/MS. Regardless of the analytical method used, the highest concentration detected exceeded the current French guideline value for brevetoxins in shellfish. To ensure consumer protection, a two-step monitoring strategy is proposed: initial screening via ELISA to estimate brevetoxin contamination, followed by confirmatory LC-MS/MS analysis to identify and quantify the specific metabolites.
Full article
(This article belongs to the Special Issue Marine Biotoxins, 4th Edition)
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Open AccessArticle
Analytical Framework to Navigate Microalgae-Based Product Development—Aligning Commercialization and Regulatory Pathways
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Galey Tenzin, Kira Schipper, Harshit Rathore, Hemil Shah, Edgar Brea, Ben Hankamer and Damian Hine
Mar. Drugs 2026, 24(2), 66; https://doi.org/10.3390/md24020066 - 3 Feb 2026
Abstract
After numerous false starts, the global microalgae industry is re-emerging, driven by its potential to address critical challenges in food and nutrition, sustainable energy, nutraceuticals, cosmetics and pharmaceuticals, and climate change mitigation. Although technical advances in microalgae production show value adding potential, progressing
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After numerous false starts, the global microalgae industry is re-emerging, driven by its potential to address critical challenges in food and nutrition, sustainable energy, nutraceuticals, cosmetics and pharmaceuticals, and climate change mitigation. Although technical advances in microalgae production show value adding potential, progressing from innovation to product launch and competitiveness is complex. It requires an integrated understanding of technology readiness, regulatory compliance, financial necessities, and market competition. This study presents a novel analytical framework underpinning a data-enabled, evidence-based approach to navigating the innovation pathways to market and beyond. The framework integrates value-add opportunities, identifying key stages faced in pre-competitive (including Technology Readiness Level (TRL), R&D spend, and patent trends), and competitive market stages (including product launches, product claims, market size, market share, growth/maturity, international markets, distribution channels, sectoral profile, and competitive landscape), aligned with regulatory requirements. Although not without limitations, such as incomplete data for emerging products, as well as reliance on secondary sources for product stage determination and market size estimates which can influence the accuracy of TRL classification and market potential estimates. This integration of multiple analyses can help in identifying market opportunities and business competitiveness via product, business, and industry level analyses in the pre-competitive (pre-market launch) and competitive (on market) landscapes. Building on the team’s interdisciplinary experience of developing interactive dashboards for food and beverage industries, and microalga processes, this paper provides an overview of the framework, which was designed to guide businesses and researchers in an emerging microalgae industry through the complex landscape of product development along regulatory and commercial pathways.
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(This article belongs to the Special Issue From Marine Natural Products to Marine Bioproducts)
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Open AccessArticle
A Novel Cobalt-Activated Halotolerant α-Amylase with High Specific Activity from Priestia sp. W243 in Kuwait Sabkha for Biotechnological Applications
by
Surendraraj Alagarsamy, Sabeena Farvin Koduvayur Habeebullah, Ismail Saheb Azad, Saja Adel Fakhraldeen, Turki Al Said, Aws Al Ghuniam and Faiza Al-Yamani
Mar. Drugs 2026, 24(2), 65; https://doi.org/10.3390/md24020065 - 3 Feb 2026
Abstract
Sabkhas, hypersaline ecosystems along Kuwait’s coastal zone, are extreme environments that harbor diverse halophilic microorganisms with significant biotechnological potential. Despite this, they remain underexplored, particularly in the context of enzymes that can function under high salinity. The aim of this study is to
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Sabkhas, hypersaline ecosystems along Kuwait’s coastal zone, are extreme environments that harbor diverse halophilic microorganisms with significant biotechnological potential. Despite this, they remain underexplored, particularly in the context of enzymes that can function under high salinity. The aim of this study is to identify bacterial isolates from Kuwait’s sabkhas that produce α-amylase under extreme environmental conditions and to purify and characterize the resulting halotolerant α-amylase. Among the seven α-amylase-producing isolates, Priestia sp. W243, isolated from Mina Abdullah, exhibited the highest enzyme production under optimal growth conditions of pH 9.0, 37 °C, and 7.5% NaCl. A novel halotolerant α-amylase with a remarkably high specific activity (8112.1 U/mg) was purified from this isolate using ultrafiltration, ion-exchange chromatography, and gel-filtration. The purified enzyme, with a molecular weight of 25 kDa, showed optimal activity at 40 °C, pH 8, and 3% NaCl. Notably, the enzyme remained active in the absence of salt and up to 15% NaCl, demonstrating exceptional halotolerance. Metal ion profiling revealed that enzyme activity was significantly enhanced by Co2+, whereas Ca2+ had a comparatively moderate effect on enzyme activity. When the effects of metal chelators were examined, EDTA, a strong metal chelator, inhibited the enzyme. However, the enzyme remained active when Ca2+ was specifically removed using EGTA, suggesting that this α-amylase may be a cobalt-dependent metalloenzyme, which is an unusual characteristic among known α-amylases. Additionally, the enzyme retained its catalytic activity under reducing conditions (e.g., in the presence of DTT and β-mercaptoethanol), indicating structural stability is independent of disulfide bonds. These unique properties distinguish this α-amylase from typical salt- or calcium-dependent counterparts and highlight its potential for industrial applications in high-salt food processing, baking, brewing, and environmental remediation.
Full article
(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)
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Open AccessArticle
Fucoidan from Fucus vesiculosus Protects Retinal Pigment Epithelium from Lipid-Induced Damage Related to AMD
by
Femke Hacker, Johann Roider, Alexa Klettner and Philipp Dörschmann
Mar. Drugs 2026, 24(2), 64; https://doi.org/10.3390/md24020064 - 2 Feb 2026
Abstract
Fucoidans are natural compounds that exhibit bioactivity against age-related macular degeneration (AMD), the leading cause of central vision loss in industrialized nations. Pathological factors like oxidative stress and lipid peroxidation play vital roles in AMD pathogenesis. Lipid-induced alterations in the retinal pigment epithelium
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Fucoidans are natural compounds that exhibit bioactivity against age-related macular degeneration (AMD), the leading cause of central vision loss in industrialized nations. Pathological factors like oxidative stress and lipid peroxidation play vital roles in AMD pathogenesis. Lipid-induced alterations in the retinal pigment epithelium (RPE) contribute to AMD development. In this study, a commercial fucoidan from Fucus vesiculosus (FVs) was tested for its activity regarding lipid-peroxidation-related effects. The human RPE cell line ARPE-19, primary porcine RPE, and RPE/choroid explants were stimulated with erastin, acting as an inducer of lipid peroxidation, and treated with fucoidan. Effects on cell viability (tetrazolium bromide (MTT) or calcein staining), vascular endothelial growth factor (VEGF) and interleukin 8 (IL8) secretion (ELISA), reactive oxygen species (ROS), protein expression (glutathione peroxidase 4 (GPX4), CD59, and retinoid isomerohydrolase (RPE65), analyzed via Western blot), and gene expression (RT-qPCR) were investigated. FVs showed protective effects against erastin-induced reduction in viability (with a 12.7% increase in viability compared to erastin), RPE65 expression (with a 4.2-fold increase compared to erastin), and GPX4 expression (with a 2.3-fold increase compared to erastin) in primary RPE. Erastin-induced VEGF secretion was attenuated by FVs in ARPE-19 and primary RPE (with an up to 1.7-fold reduction compared to erastin). Elevated IL8 levels were reduced by FV treatment in primary RPE (with a 9.1-fold reduction compared to erastin). Induced VEGF in RPE/choroid explants was reduced by FVs (with an up to 2.9-fold reduction compared to erastin), and this reduction was correlated with slight improvements in viability. In conclusion, FVs exerted protective effects against lipid-induced stress. This study reveals further effects of fucoidans against AMD-related pathologies.
Full article
(This article belongs to the Special Issue Marine-Derived Bioactive Compounds with Potential Applications for Retinal Health)
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Open AccessArticle
Concise Synthesis and Biological Evaluation of a Phorbazole Analogue-B1 Identifies a Multi-Kinase Inhibitor with Anti-AML Activity
by
Xiang Chen, Liting Zhang, Jinqi Huang, Mingzhi Su, Yuewei Guo and Xin Jin
Mar. Drugs 2026, 24(2), 63; https://doi.org/10.3390/md24020063 - 2 Feb 2026
Abstract
Phorbazoles are bioactive marine alkaloids whose development is hampered by limited supply. We report a concise synthesis of the deschloro-phorbazole core via an optimized iodine-catalyzed oxazole annulation (56% yield). This route enabled efficient access to the scaffold and the preparation of analog B1
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Phorbazoles are bioactive marine alkaloids whose development is hampered by limited supply. We report a concise synthesis of the deschloro-phorbazole core via an optimized iodine-catalyzed oxazole annulation (56% yield). This route enabled efficient access to the scaffold and the preparation of analog B1. B1 showed nanomolar cytotoxicity (IC50 = 0.04 µM) against MV4-11 leukemia cells by inducing G0/G1 arrest (via cyclin D1/CDK6 downregulation) and apoptosis. As a multi-kinase inhibitor, B1 also potently inhibited endothelial network formation and migration, demonstrating anti-angiogenic activity. This work provides an efficient synthetic strategy and identifies B1 as a promising dual-function anticancer lead compound.
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(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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Open AccessArticle
Corallomycetellains A–J, Cytotoxic Epipolythiodioxopiperazine Alkaloids Isolated from the Fungi Corallomycetella repens HDN23-0007
by
Chenqi Zhang, Luning Zhou, Shuo Zhao, Wenxue Wang, Xiaomin Zhang, Qian Che, Tianjiao Zhu, Mei Han and Dehai Li
Mar. Drugs 2026, 24(2), 62; https://doi.org/10.3390/md24020062 - 1 Feb 2026
Abstract
Ten new epipolythiodioxopiperazine (ETP) alkaloids, named corallomycetellains A–J (1–10), along with one known analogue, haematocin (11), were isolated from the fungi Corallomycetella repens HDN23-0007. Their structures, including absolute configurations, were established by comprehensive spectroscopic data and electronic
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Ten new epipolythiodioxopiperazine (ETP) alkaloids, named corallomycetellains A–J (1–10), along with one known analogue, haematocin (11), were isolated from the fungi Corallomycetella repens HDN23-0007. Their structures, including absolute configurations, were established by comprehensive spectroscopic data and electronic circular dichroism (ECD) calculations. Compounds 1–2 represent the first two examples of aranotin-type ETPs possessing an aromatic indole moiety. Compounds 2–4 all featured a unique C2-methyl disulfide substituent, whereas compound 4 additionally possessed a C2′-oxomethyl group. In in vitro cytotoxicity assays, compounds 7–10, which contained α–α′ polysulfide bridges, exhibited strong anticancer activity, with IC50 values ranging from 1.1 to 9.3 μM.
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(This article belongs to the Section Structural Studies on Marine Natural Products)
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Open AccessReview
Smart Secondary Metabolites in Marine Environments: The Case of Elatol
by
Angélica R. Soares, Nathalia Nocchi, Ana R. Díaz-Marrero, Renato C. Pereira and José J. Fernández
Mar. Drugs 2026, 24(2), 61; https://doi.org/10.3390/md24020061 - 1 Feb 2026
Abstract
The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and
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The concept of “Smart Secondary Metabolites” is introduced here to describe a privileged class of natural products defined by structural originality, biosynthetic adaptability, and broad interaction potential with biological systems. Elatol, a halogenated sesquiterpene chiefly produced by Laurencia red seaweeds and occasionally accumulated by their consumers, exemplifies this concept with remarkable clarity. Its biosynthesis unfolds from farnesyl diphosphate via γ-bisabolane cations, bromochlorination, and stereoselective cyclization to chamigrene scaffolds, generating both (+)- and (–)-enantiomers, two metabolites with clearly distinct potential ecological roles and pharmacological profiles. This review synthesizes the current state of knowledge on elatol’s distribution, biosynthetic origins, ecological relevance, and therapeutic potential. Elatol serves as a multifunctional chemical mediator, fulfilling defensive, communicative, and regulatory roles whose intensity shifts in response to herbivory, biofouling, temperature, and salinity. In parallel, its potent activities against infectious, metabolic, and neoplastic diseases highlight its growing value as a drug lead, reflected in a rising number of patent claims. Altogether, elatol emerges as a model Smart Secondary Metabolite whose ecological sophistication and biochemical versatility position it as a promising scaffold for marine-derived drug discovery.
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(This article belongs to the Special Issue Pharmacognostic Potential of Seaweed Extracts and Metabolites)
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Open AccessArticle
Optimisation of Alginate Extraction and Characterisation of Polysaccharides from Brown Seaweed from the Portuguese Coast
by
Joana Corrêa Mendes, Joana F. A. Valente, Fani Sousa, Raul Bernardino, Susana Bernardino, Clélia Afonso and Bárbara Chagas
Mar. Drugs 2026, 24(2), 60; https://doi.org/10.3390/md24020060 - 1 Feb 2026
Abstract
Alginate is a widely used and versatile biopolymer with an ever-expanding range of applications in the pharmaceutical and biomedical industries. This highlights the importance of developing sustainable and renewable production sources. Conventional extraction methods, although effective, are often energy-intensive and rely on harsh
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Alginate is a widely used and versatile biopolymer with an ever-expanding range of applications in the pharmaceutical and biomedical industries. This highlights the importance of developing sustainable and renewable production sources. Conventional extraction methods, although effective, are often energy-intensive and rely on harsh chemicals. In this context, brown algae are a promising alternative due to their abundance and renewability. This study investigated the potential of Saccorhiza polyschides and Sargassum muticum as sources of sodium alginate (SA), thus optimising an extraction process that combines acid treatment with an alkaline step. The extracted biopolymers were characterised using FTIR, H-NMR, STA, SEM/EDX, viscosity measurements, dynamic light scattering, and spectrophotometric assays of residual polyphenols and proteins. The optimised extraction conditions produced yields above 20% of high-purity alginate. When compared with commercial SA, the extracted materials showed comparable quality while relying on a simplified, solvent-reduced protocol that improves process efficiency and reduces the environmental impact. These results demonstrate that S. polyschides and S. muticum are promising, locally available sources of high-quality sodium alginate, and that industrially relevant yields (>20%) can be achieved through an environmentally conscious two-step extraction process.
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(This article belongs to the Special Issue Marine Polysaccharides-Based Biomaterials)
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Peptide Modulator of TRPV1 Channel Increases Long-Term Potentiation in the Hippocampus and Reduces Anxiety and Fear in Mice Under Acute Stress
by
Vladimir M. Pavlov, Anastasia Yu. Fedotova, Victor A. Palikov, Yulia A. Logashina, Kamilla I. Zagitova, Igor A. Dyachenko, Alexander V. Popov and Yaroslav A. Andreev
Mar. Drugs 2026, 24(2), 59; https://doi.org/10.3390/md24020059 - 31 Jan 2026
Abstract
One of the attractive targets for the relief of stress conditions is TRPV1, which is expressed mostly in primary afferent neurons (nociceptors) and in the central nervous system, mainly in the cortex and hippocampus. We evaluated the action of a potent low-molecular-weight antagonist
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One of the attractive targets for the relief of stress conditions is TRPV1, which is expressed mostly in primary afferent neurons (nociceptors) and in the central nervous system, mainly in the cortex and hippocampus. We evaluated the action of a potent low-molecular-weight antagonist of TRPV1 (AMG517) and peptide modulator of this channel (APHC3) on long-term potentiation (LTP) and Paired-Pulse Ratio (PPR) in the CA3-CA1 region of the hippocampus of mice. In vivo, we used intranasal administration to provide effective peptide delivery into the brain and analyzed the effects of APHC3 in acute stress tests in comparison with intramuscular administration of APHC3, AMG517, and the reference anxiolytic drug Fabomotizole (Fab). In electrophysiology studies, APHC3 significantly enhanced LTP and PPR, while AMG517 enhanced only PPR. Intranasal administration of APHC3 to mice provided a moderate anxiolytic effect in the single dose (0.01 mg/kg). Intramuscular administration of APHC3 and AMG517 significantly reduced acute stress in mice equal to the reference drug Fab. Thus, TRPV1 modulation in either the peripheral or central nervous system is sufficient to produce an anxiolytic-like effect, likely through distinct underlying mechanisms.
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(This article belongs to the Section Marine Pharmacology)
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Open AccessArticle
Deep-Sea Marine Metabolites as Promising Anti-Tubercular Agents: CADD-Guided Targeting of the F420-Dependent Oxidoreductase
by
Ria Desai, Amane A. Alaroud, Gagan Preet, Rishi Vachaspathy Astakala, Rainer Ebel and Marcel Jaspars
Mar. Drugs 2026, 24(2), 58; https://doi.org/10.3390/md24020058 - 31 Jan 2026
Abstract
Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a leading global threat, escalated now by the rise of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. In search of a novel anti-tubercular agent with a distinct mechanism of action, this study explores deep-sea marine
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Tuberculosis, caused by Mycobacterium tuberculosis (M. tb), remains a leading global threat, escalated now by the rise of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains. In search of a novel anti-tubercular agent with a distinct mechanism of action, this study explores deep-sea marine metabolites as potential inhibitors of the F420-dependent oxidoreductase Rv1155, a redox enzyme essential for M. tb survival. A total of 2773 marine-derived compounds curated from the CMNPD, Reaxys, and MarinLit databases were screened using an integrated CADD workflow combining molecular docking, in-silico ADMET profiling, and molecular dynamics (MD) simulations. Docking identified 68 metabolites with strong affinity (−10.98 to −15.95 kcal/mol) for the Rv1155 binding pocket, and from which three compounds, Upenamide (CMNPD_22964), Aspyronol (Compound_1749), and Fiscpropionate F (Compound_1796), were shortlisted as hit candidates. Among these, Upenamide displayed the strongest binding (ΔG = −28.56 kcal/mol) with stable RMSD and hydrogen bond persistence during 100 ns MD simulation, while Aspyronol demonstrated a promising ADMET profile comparable to the native cofactor F4202. MM-GBSA analysis further confirmed the strong binding strength (ΔG _bind = −24.77 to −34.07 kcal/mol) for all three hit candidates. These findings confirm the strong and stable interaction of selected deep-sea marine metabolites with Rv1155. This validated screening pipeline established here provides a cost-effective framework for future experimental validation and expansion to additional F420-related drug targets in M. tb.
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(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)
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Botryococcene Inhibits UV-B-Induced Photoaging by Scavenging Intracellular Reactive Oxygen Species
by
Hiromi Kurokawa and Makoto M. Watanabe
Mar. Drugs 2026, 24(2), 57; https://doi.org/10.3390/md24020057 - 30 Jan 2026
Abstract
Sunlight exposure contributes to human health; however, excessive light exposure to skin, especially ultraviolet B (UV-B), can produce high amounts of reactive oxygen species (ROS) and induce inflammation. Some antioxidants, such as squalene, can prevent UV-B-induced inflammation. C34H58 botryococcene is
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Sunlight exposure contributes to human health; however, excessive light exposure to skin, especially ultraviolet B (UV-B), can produce high amounts of reactive oxygen species (ROS) and induce inflammation. Some antioxidants, such as squalene, can prevent UV-B-induced inflammation. C34H58 botryococcene is the most common triterpene hydrocarbon produced by green alga Botryococcus braunii; it is biosynthesized via a pathway similar to squalene and appears to have a similar chemical structure to squalene. However, there are no reports on the bioactivity of botryococcene. In this study, we evaluated that botryococcene can prevent the skin photoaging. Using ESR assay, botryococcene could not scavenge any ROS. However, treatment of epidermis cells with the botryococcene significantly suppressed intracellular ROS production by hydrogen peroxide (H2O2) and attenuated H2O2 cytotoxicity. Botryococcene enhanced the antioxidant enzymes in gastric cells, thus botryococcene may scavenge ROS indirectly, not directly. Moreover, botryococcene inhibited production of intracellular interleukin-1 and exhibited suppression of melanogenesis activity by UV-B irradiation. Addition of botryococcene-treated epidermal cells culture medium mitigated the increase in matrix metalloproteinase-1 production and the decrease in type I collagen production induced by UV-B irradiation in dermis cells. These results showed that botryococcene has anti-photoaging effects, including preventing wrinkles and blemishes on the skin.
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(This article belongs to the Special Issue Algae-Powered Skincare: Innovations in Marine-Derived Cosmeceuticals)
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