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Mar. Drugs, Volume 24, Issue 2 (February 2026) – 34 articles

Cover Story (view full-size image): Smart Secondary Metabolites are natural products defined by structural originality, biosynthetic flexibility, ecological relevance, and broad biological interactions. Elatol, a halogenated chamigrane sesquiterpene produced mainly by Laurencia red seaweeds and sometimes accumulated by their consumers, exemplifies this concept. Forged by marine evolution and shaped by ecological pressures to mediate defense, signaling, and species interactions, elatol embodies adaptive chemical versatility. Its multifunctionality extends beyond the ocean, revealing wide pharmacological promise and biotechnological potential. With its rare architecture, stereochemical complexity, and distinctive biosynthetic origin, elatol emerges as a paradigm of evolutionary chemical innovation, linking environment, metabolism, and function. View this paper
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21 pages, 6142 KB  
Article
Anti-Photoaging Effects of a Polysaccharide from Kappaphycus alvarezii In Vitro and In Vivo
by Yixuan Lai, Yuan Wang, Abdul Mueed, Peng Shu, Lijun You and Jiangming Zhong
Mar. Drugs 2026, 24(2), 87; https://doi.org/10.3390/md24020087 - 21 Feb 2026
Viewed by 362
Abstract
The red alga Kappaphycus alvarezii is a rich source of polysaccharides, but their high molecular weight limits skin permeability and bioavailability. To address this, we employed a free-radical degradation method to produce a low-molecular-weight polysaccharide, KP-90. Evaluation in UVB-irradiated HaCaT cells and UVA-irradiated [...] Read more.
The red alga Kappaphycus alvarezii is a rich source of polysaccharides, but their high molecular weight limits skin permeability and bioavailability. To address this, we employed a free-radical degradation method to produce a low-molecular-weight polysaccharide, KP-90. Evaluation in UVB-irradiated HaCaT cells and UVA-irradiated human dermal fibroblasts demonstrated that KP-90 significantly enhanced cell viability and mitigated oxidative stress by suppressing reactive oxygen species and malondialdehyde, while restoring antioxidant enzymes (SOD, CAT and GSH-Px). Furthermore, KP-90 downregulated matrix metalloproteinases (MMP-1, -3, -9) and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), thereby reducing extracellular matrix degradation and inflammation. These in vitro findings were corroborated in a UVB/UVA-irradiated nude mice model, where KP-90 alleviated epidermal hyperplasia, increased collagen I and hyaluronic acid synthesis, and improved visible signs such as wrinkles and skin laxity. These findings identify KP-90 against skin photoaging and provide a strategic approach for valorization underexploited marine biomass. Full article
(This article belongs to the Special Issue Marine Compounds as Cosmetic Ingredients)
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16 pages, 1171 KB  
Article
Marine Microalga Tisochrysis lutea F&M-M36 Modulates Gut Microbiota and Intestinal Cholesterol Transport Gene Expression in Association with Selected Early-Stage Metabolic Alterations Under High-Fat Feeding
by Elisabetta Bigagli, Niccolò Meriggi, Mario D’Ambrosio, Natascia Biondi, Liliana Rodolfi, Alberto Niccolai, Gianluca Bartolucci, Marta Menicatti, Carlotta de Filippo and Cristina Luceri
Mar. Drugs 2026, 24(2), 86; https://doi.org/10.3390/md24020086 - 21 Feb 2026
Viewed by 255
Abstract
Modulation of the gut microbiota represents a promising approach to counteract diet-induced metabolic alterations, with microalgae emerging as potential interventions. Building on our previous in vivo evidence that dietary supplementation with the marine microalga Tisochrysis lutea F&M-M36 (T. lutea) positively modulates [...] Read more.
Modulation of the gut microbiota represents a promising approach to counteract diet-induced metabolic alterations, with microalgae emerging as potential interventions. Building on our previous in vivo evidence that dietary supplementation with the marine microalga Tisochrysis lutea F&M-M36 (T. lutea) positively modulates selected metabolic alterations under high-fat feeding, the present study aimed to identify potential associations between these metabolic changes and coordinated modifications of the gut microbiota. Animals were fed normal-fat (NF), high-fat (HF), or HF supplemented with 5% T. lutea (HFTiso) diets for three months. Gut microbial profiles were analyzed by 16S rRNA sequencing and correlated with plasma lipids, glucose, blood pressure, fecal lipid excretion, and adiponectin levels. T. lutea supplementation was associated with significant modulation of selected metabolic parameters and coherent alterations in gut microbial communities. Multivariate analyses revealed treatment-dependent clustering of metabolic profiles, with HFTiso forming an intermediate group between HF and NF diets. Beta-diversity analyses showed marked treatment-specific shifts, while alpha-diversity remained stable. Linear discriminant analysis identified 31 discriminative genera, with the HFTiso group enriched in taxa associated with fermentative metabolism and lipid-related metabolic pathways including Anaerotruncus, Marvinbryantia, and Eubacterium coprostanoligenes, while the HF group was linked to Clostridium sensu stricto 1 and Terrisporobacter. Positive correlations between HFTiso-associated taxa and adiponectin levels were consistent with microbiota-associated metabolic signatures. In parallel, T. lutea supplementation was associated with downregulation of colonic Niemann-Pick C1-like 1 (NPC1L1) mRNA expression, a key mediator of intestinal cholesterol uptake. The bioactivity of T. lutea likely reflects its content of polyunsaturated fatty acids, oleic acid, phytosterols, and fucoxanthin; however, whether these components act synergistically or whether specific bioactive compounds are primarily responsible remains to be clarified. Together, these findings indicate that T. lutea supplementation is associated with coordinated changes in gut microbiota composition and transcriptional modulation of the intestinal cholesterol transporter NPC1L1 in the context of selected early-stage metabolic alterations under high-fat feeding. While direct extrapolation to humans remains limited, these results suggest potential translational relevance of T. lutea as a nutraceutical approach targeting early-stage metabolic dysregulation. Future studies will be required to determine the mechanistic contribution of individual bioactive components and to assess whether microbiota- and gene expression-associated changes play a causal role in mediating the observed metabolic outcomes, thereby informing the rational development of T. lutea-derived interventions. Full article
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21 pages, 2080 KB  
Article
Posidonia oceanica (L.) Delile as a Marine Anti-Inflammatory Modulator of Keratinocyte Inflammatory Responses Relevant to Psoriasis
by Marzia Vasarri, Donatella Degl’Innocenti, Matteo Lulli, Nicola Schiavone, Alice Verdelli, Marzia Caproni, Emiliano Antiga and Emanuela Barletta
Mar. Drugs 2026, 24(2), 85; https://doi.org/10.3390/md24020085 - 19 Feb 2026
Viewed by 449
Abstract
Skin inflammation is characterized by oxidative stress, excessive keratinocyte activation, and the overproduction of pro-inflammatory cytokines. In a previous study, we demonstrated that the hydroalcoholic extract from Posidonia oceanica leaves (POE) mitigates psoriasis-like skin inflammation in a mouse model. In the present study, [...] Read more.
Skin inflammation is characterized by oxidative stress, excessive keratinocyte activation, and the overproduction of pro-inflammatory cytokines. In a previous study, we demonstrated that the hydroalcoholic extract from Posidonia oceanica leaves (POE) mitigates psoriasis-like skin inflammation in a mouse model. In the present study, we investigated the cellular mechanisms underlying these effects in human HaCaT keratinocytes. Non-cytotoxic lipopolysaccharide (LPS) stimulation reproduced key inflammatory features, including impaired cell proliferation, increased production of ROS and NO, and the upregulation of IL-1β, IL-6, TNF-α and CXCL8/IL-8. Co-treatment with POE significantly attenuated these alterations by restoring cell proliferation, suppressing oxidative stress, particularly NOS2/NO, and normalizing both cytokine expression and release. POE alone did not affect cell viability or inflammatory markers, confirming its favorable safety profile. However, POE alone induced a mild pro-apoptotic response, which may contribute to overcoming the apoptosis resistance typically observed in psoriatic keratinocytes. Overall, these findings demonstrate that POE exerts antioxidant and anti-inflammatory effects in activated keratinocytes and support its potential as a marine-derived candidate for complementary strategies in the management of psoriasis-associated inflammatory skin disorders. Full article
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18 pages, 3596 KB  
Article
Synthesis, Biological Evaluation, and Computational Studies of Phenolic N-Acetylglucosamine Glycosides as α-Glucosidase Inhibitors
by Wenjie Wang, Kun Gao, Guantian Li, Zongji Wang, Kecheng Li, Song Liu, Huahua Yu and Ronge Xing
Mar. Drugs 2026, 24(2), 84; https://doi.org/10.3390/md24020084 - 19 Feb 2026
Viewed by 368
Abstract
Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic metabolic diseases, and inhibition of α-glucosidase activity represents an effective therapeutic strategy. Chitin is the most abundant renewable polysaccharide in the ocean, with its monosaccharide being N-acetylglucosamine (NAG). To evaluate [...] Read more.
Type 2 diabetes mellitus (T2DM) is one of the most prevalent chronic metabolic diseases, and inhibition of α-glucosidase activity represents an effective therapeutic strategy. Chitin is the most abundant renewable polysaccharide in the ocean, with its monosaccharide being N-acetylglucosamine (NAG). To evaluate the potential of NAG glycosides as novel α-glucosidase inhibitors, three common phenolic compounds were modified via NAG glycosylation. Their inhibitory activities were assessed at both the enzymatic and cellular levels. In addition, density functional theory (DFT), molecular dynamics (MD) simulations, and molecular docking analyses were employed to systematically investigate the effects of NAG glycosylation on enzyme inhibition and the underlying mechanisms. Compared with the parent phenolic compounds, NAG glycosides exhibited significantly enhanced α-glucosidase inhibitory activity, with NAG introduction markedly improving their binding affinity to α-glucosidase. Among them, glycoside 3a displayed the optimal inhibitory effect, comparable to acarbose, and at the cellular level, its activity at high concentrations was comparable to or slightly higher than that of metformin. Circular dichroism (CD) and MD analyses indicated that glycoside 3a increased the conformational flexibility of key residues and enhanced the structural looseness of the enzyme, thereby inhibiting its activity. NAG glycosides constitute a promising class of marine-derived α-glucosidase inhibitors, warranting further structural optimization and rational design to enhance their activity and selectivity. Full article
(This article belongs to the Special Issue Marine Glycobiology)
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22 pages, 1436 KB  
Article
Synergistic Effects of Light and Salinity on Carotenoid and Biomass Composition of Synechocystis PCC6803 Cultures
by Cecilia Faraloni, Gergely Erno Lakatos, Francesco Balestra, Anna Pugliese, Graziella Chini Zittelli, Bernardo Cicchi, Eleftherios Touloupakis and Giuseppe Torzillo
Mar. Drugs 2026, 24(2), 83; https://doi.org/10.3390/md24020083 - 19 Feb 2026
Viewed by 448
Abstract
Light and salt stress affect the growth of plants and microorganisms, causing photo-oxidative stress. The cyanobacterium Synechocystis is notable for its adaptability to and sustainability in seawater. In this study, the synergistic effects of different light intensities and salt concentrations on the growth [...] Read more.
Light and salt stress affect the growth of plants and microorganisms, causing photo-oxidative stress. The cyanobacterium Synechocystis is notable for its adaptability to and sustainability in seawater. In this study, the synergistic effects of different light intensities and salt concentrations on the growth and biomass composition of Synechocystis were examined. Cultures were grown in BG11 medium (control) and with 20 and 40 g L−1 marine salts (obtained from a commercial sea water preparation) at 100, 200, and 400 μmoles photons m−2 s−1 (LL, ML, and HL, respectively) to assess the interactive effects of salinity stress and increasing light intensity. The effect of salinity stress was most pronounced under LL and ML, where the highest accumulation of all major carotenoids was observed; under HL, the contents of most carotenoids significantly increased mainly at the highest salt concentration but to a lesser extent). Under LL and ML echinenone reached the highest values (2.71-fold and 3.75-fold higher than in the control, respectively), whereas β-carotene showed the highest increase at LL, reaching concentrations three times those of the control. At HL myxoxanthophyll exhibited the highest increase with marine salt (1.9-fold higher than in the control). The results show that Synechocystis could grow at all light intensities and marine salt concentrations via increased synthesis of carotenoids in response to physiological stress. Full article
(This article belongs to the Special Issue Algal Cultivation for Obtaining High-Value Products, 2nd Edition)
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25 pages, 5881 KB  
Article
Integrative Metabolomics and Systems Pharmacology Reveal PPARγ-Centered Antidiabetic Mechanisms of Caulerpa racemosa and Its Bioactive Compounds
by Fahrul Nurkolis, Annette d’Arqom, Evhy Apryani, Nurmawati Fatimah, Adha Fauzi Hendrawan, Izza Afkarina, Reggie Surya, Happy Kurnia Permatasari, Dante Saksono Harbuwono, Nurpudji Astuti Taslim, Arifa Mustika and Raymond Rubianto Tjandrawinata
Mar. Drugs 2026, 24(2), 82; https://doi.org/10.3390/md24020082 - 17 Feb 2026
Viewed by 477
Abstract
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring safe, multitarget therapeutic strategies. Marine macroalgae represent an underexplored source of bioactives with pleiotropic metabolic effects. This study investigated the antidiabetic potential of an ultrasound-assisted ethanolic extract of Caulerpa racemosa (UAECr) and [...] Read more.
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder requiring safe, multitarget therapeutic strategies. Marine macroalgae represent an underexplored source of bioactives with pleiotropic metabolic effects. This study investigated the antidiabetic potential of an ultrasound-assisted ethanolic extract of Caulerpa racemosa (UAECr) and its key phytosterol, campesterol, through an integrative framework combining metabolomics, network pharmacology, molecular docking, molecular dynamics simulation, and in vitro validation. Untargeted ultra-high-performance liquid chromatography–high-resolution mass spectrometry (UHPLC–HRMS) metabolomics characterized UAECr constituents, followed by in silico bioactivity prediction, target-network analysis, molecular docking, and 100 ns molecular dynamics simulation of the peroxisome proliferator-activated receptor gamma (PPARγ)–campesterol complex. Functional validation was performed in differentiated 3T3-L1 adipocytes assessing glucose uptake, PPARγ expression, dipeptidyl peptidase 4 (DPP-4) inhibition, and cytotoxicity. Metabolomics identified campesterol as a prominent bioactive. Network pharmacology highlighted PPARγ as a central hub, supported by strong docking affinity of campesterol toward PPARγ (−11.4 kcal/mol) and DPP-4 (−8.3 kcal/mol). Molecular dynamics simulations demonstrated stable PPARγ–campesterol interactions, with preserved protein compactness and low residue fluctuation. In vitro, UAECr and campesterol significantly enhanced glucose uptake (up to 134% vs. control, p < 0.001), upregulated PPARγ expression (4-fold, p < 0.0001), and moderately inhibited DPP-4 activity (p < 0.01) without cytotoxicity. C. racemosa-derived extracts and campesterol exert antidiabetic effects primarily via stable PPARγ-mediated insulin sensitization with complementary DPP-4 modulation, supporting its potential as a marine-derived functional food candidate. Full article
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17 pages, 1811 KB  
Article
Harnessing Biogas into High-Value Chemicals: The Role of Algal–Methanotrophic Co-Cultures
by Rebecca Serna-García, Ysis Lanzoni, Octavio García-Depraect, Raul Muñoz and Sara Cantera
Mar. Drugs 2026, 24(2), 81; https://doi.org/10.3390/md24020081 - 17 Feb 2026
Viewed by 519
Abstract
The conversion of biogas into high-value chemicals for pharmaceutical, cosmetic, and nutraceutical markets offers an attractive alternative to conventional fossil-based production routes, enabling circular value chains with significant socio-economic impact. This study evaluated the valorization of biogas into osmolyte and carotenoid compounds with [...] Read more.
The conversion of biogas into high-value chemicals for pharmaceutical, cosmetic, and nutraceutical markets offers an attractive alternative to conventional fossil-based production routes, enabling circular value chains with significant socio-economic impact. This study evaluated the valorization of biogas into osmolyte and carotenoid compounds with market prices ranging from 1000 to 7000 $·kg−1. Specifically, an algal–methanotrophic co-culture operated under saline conditions, preventing external microbial contamination and stimulating osmolytes and carotenoids, was assessed for its capacity to simultaneously remove methane (CH4) and carbon dioxide (CO2), with efficiencies of 92 and 89%, respectively. while producing ectoine, hydroxyectoine, lutein, β-carotene, and astaxanthin. Shotgun metagenomic analyses identified the key microorganisms driving the process, predominantly alkaliphilic and halophilic green algae (Chlorella, Dunaliella) and cyanobacteria (Leptolyngbya), and halotolerant methanotrophs (Methylotuvimicrobium) and methylotrophs (Methylophaga). Metagenomics further revealed the presence of key metabolisms related to C1 utilization and biosynthetic genes associated with carotenoid and osmolyte production, confirming the metabolic potential of the consortium to convert biogas-derived carbon directly into high-value compounds. Overall, these results demonstrate the feasibility of an efficient, biologically driven bio-platform capable of transforming greenhouse gas-rich waste streams into economically relevant bioactive molecules, contributing to global priorities in sustainable biomass-to-biochemical innovation. Full article
(This article belongs to the Special Issue Synthetic Biology in Marine Microalgae)
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13 pages, 1749 KB  
Article
Diverse and Bioactive Lactones from the Sri Lankan Mangrove-Derived Fungus Talaromyces sp. SCSIO41445
by Parakkrama Wijerathna, Xinqi Chen, Yi Chen, Yufan Zhang, Jian Cai, Mengjing Cong, Ying Liu, Lalith Jayasinghe, Yonghong Liu, Disna Ratnasekera and Xuefeng Zhou
Mar. Drugs 2026, 24(2), 80; https://doi.org/10.3390/md24020080 - 14 Feb 2026
Viewed by 335
Abstract
Three previously uncharacterized lactones, namely penicianstinoid L (1), talaromyketide J (2) and peniciisocoumarin K (3), along with twenty-eight known compounds (431), were yielded from the mangrove-derived fungus Talaromyces sp. SCSIO41445, collected from Mangrove [...] Read more.
Three previously uncharacterized lactones, namely penicianstinoid L (1), talaromyketide J (2) and peniciisocoumarin K (3), along with twenty-eight known compounds (431), were yielded from the mangrove-derived fungus Talaromyces sp. SCSIO41445, collected from Mangrove Park (NARA), Sri Lanka. Their structures were established by HRESIMS and NMR spectroscopic analysis (including 1H and 13C NMR, HSQC, and HMBC), with the stereostructures of 2 and 3 being confirmed by single-crystal X-ray crystallographic analysis. Furthermore, compounds 131 were evaluated in terms of their neuraminidase (NA) inhibitory activities. These bioassay results revealed that three lactones (11, 15, and 16) of them exerted NA inhibitory effects, with IC50 values of 46.66 ± 2.31, 20.78 ± 1.89, and 34.14 ± 2.56 µM, respectively. Moreover, molecular docking analysis demonstrated the potential of these compounds to inhibit NA enzymes, revealing specific interactions between the compounds and target proteins. Full article
(This article belongs to the Special Issue Marine Microorganisms Bioprospecting, 2nd Edition)
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23 pages, 1208 KB  
Review
Phaeodactylum tricornutum as a Chassis: Insights into Its Potential, Challenges, and Perspectives
by Sen Wang, Yunuo Hao, Tengsheng Qiao, Ruihao Zhang, Deliang Yu, Hailiang Wang, Yongliang Liu, Yuhao Sun, Di Xu, Xiaojin Song and Kehou Pan
Mar. Drugs 2026, 24(2), 79; https://doi.org/10.3390/md24020079 - 13 Feb 2026
Viewed by 651
Abstract
Phaeodactylum tricornutum is one of the most well-characterized microalgae and serves as a pivotal model diatom in global carbon fixation and the mediation of biogeochemical cycling of essential nutrients. Over the past few decades, the availability of a complete genome assembly, coupled with [...] Read more.
Phaeodactylum tricornutum is one of the most well-characterized microalgae and serves as a pivotal model diatom in global carbon fixation and the mediation of biogeochemical cycling of essential nutrients. Over the past few decades, the availability of a complete genome assembly, coupled with the development of robust DNA manipulation tools and efficient DNA delivery methodologies, has established P. tricornutum as a promising photosynthetic chassis for the sustainable bioproduction of high-value compounds, including fucoxanthin and eicosapentaenoic acid (EPA). This review systematically summarizes the research progress in the strain improvement toolkit of P. tricornutum, encompassing both genetic and non-genetic engineering strategies. It elaborates on the types and applications of its representative bioactive products, as well as the molecular mechanisms underlying key synthetic pathways. Additionally, this work synthesizes the research findings on the optimization of critical cultivation conditions (e.g., light, temperature, and nutrient composition) that modulate the growth and product synthesis of P. tricornutum. On this basis, the challenges encountered by P. tricornutum in industrial applications are proposed for further discussion, aiming to provide a reference for in-depth exploration of related research directions and facilitate the expansion of its application scope in the field of biomanufacturing. Full article
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20 pages, 1750 KB  
Article
Enhanced Production of Bioactive Polyunsaturated Fatty Acids and Pigments in Rhodosorus marinus: Optimization of Thermal and Photic Stress Conditions
by Wen-Ping Cheng, Han-Yang Yeh, Yen-Ling Chen, Yi-Jung Chen, Fat-Tin Agassi Sze, Chi-Cheng Huang, Fan-Hua Nan, Ming-Chih Fang and Meng-Chou Lee
Mar. Drugs 2026, 24(2), 78; https://doi.org/10.3390/md24020078 - 13 Feb 2026
Viewed by 452
Abstract
The marine unicellular red alga Rhodosorus marinus is a promising source of the valuable phycobiliprotein phycoerythrin and essential omega-3 polyunsaturated fatty acids (PUFAs), yet the environmental triggers for their optimal co-production remain to be fully elucidated. This study was conducted to investigate the [...] Read more.
The marine unicellular red alga Rhodosorus marinus is a promising source of the valuable phycobiliprotein phycoerythrin and essential omega-3 polyunsaturated fatty acids (PUFAs), yet the environmental triggers for their optimal co-production remain to be fully elucidated. This study was conducted to investigate the effects of thermal and photic stress in terms of maximizing the yield of these high-value bioactive compounds. R. marinus was cultivated under a range of temperatures (18–24 °C) and light intensities (100–335 µmol photons m−2 s−1) to assess its physiological and biochemical responses, particularly focusing on lipid accumulation. This study investigates the effects of thermal (18–24 °C) and photic (100–335 µmol photons m−2 s−1) stress on the concurrent production of the valuable phycobiliprotein, phycoerythrin (PE), and essential omega-3 polyunsaturated fatty acids (PUFAs) in the marine red microalga Rhodosorus marinus. Fatty acid profiles were quantified using gas chromatography (GC), while pigment content was assessed via spectrophotometry. Statistical analyses, including one-way ANOVA and Tukey’s post hoc test, were employed to determine the significance of environmental effects. Our results demonstrate that a mild hypothermic condition of 18 °C significantly enhanced the production of eicosapentaenoic acid (EPA) compared to higher temperatures. Conversely, cell density was maximized at 22 °C. Under the 18 °C thermal regime, lower light intensities (100–185 µmol photons m−2 s−1) promoted a superior synthesis of both bioactive lipids and pigments. In conclusion, the strategic application of mild hypothermia combined with moderate light intensity is an effective approach to substantially boost the metabolic yield of high-value compounds in R. marinus, highlighting its potential as a sustainable source for nutraceutical and pharmaceutical applications. Full article
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23 pages, 2135 KB  
Article
Content, Ratio and Productivity of Amphidinols in Wild-Type and Mutagenized Strains of Amphidinium carterae at Different Growth Stages
by Ivan Citakovic, Gaël Bougaran, Fabienne Hervé, Damien Réveillon, Cyril El Khoury, Francis Mairet and Bruno Saint-Jean
Mar. Drugs 2026, 24(2), 77; https://doi.org/10.3390/md24020077 - 12 Feb 2026
Viewed by 382
Abstract
As agriculture faces increasing pressure to reduce pesticide residues and heavy metal accumulation in soils, marine microalgae are emerging as sustainable sources of biopesticides. Among them, Amphidinium carterae produces amphidinols (AMs), polyketide metabolites with strong antifungal activity against crop pathogens. Currently, large-scale AM [...] Read more.
As agriculture faces increasing pressure to reduce pesticide residues and heavy metal accumulation in soils, marine microalgae are emerging as sustainable sources of biopesticides. Among them, Amphidinium carterae produces amphidinols (AMs), polyketide metabolites with strong antifungal activity against crop pathogens. Currently, large-scale AM production remains constrained by a limited understanding of AM biosynthesis across different A. carterae growth phases and by the lack of high-performing industrial strains. In this study, AM production dynamics were investigated in one wild-type (WT) and five mutagenized A. carterae strains. The production of bioactive AM18 and its sulfated inactive form AM19 was monitored through exponential, linear, and early stationary growth phases. The maximum AM productivity occurred between the linear and early stationary phase, with the average values of 5.58 ± 0.4 and 3.58 ± 0.2 µg/mL/day for AM18 and AM19, respectively. The AM18/AM19 ratio consistently decreased with the culture age, indicating that earlier harvesting favors higher proportions of bioactive AMs. UV mutagenesis increased the AM18 cell content by more than twofold and the growth rate by up to 20% in certain mutagenized strains compared to the WT strain, but did not enhance the volumetric AM productivity. Overall, these results identify optimal AM harvesting windows and clarify the potential benefits of mutagenesis strain improvement for industrial AM production improvement. Full article
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36 pages, 2930 KB  
Review
From Host-Derived Pressures to the Environmental Anti-Antimicrobial Peptides Resistome: Mechanisms, Reservoirs and Implications for Therapeutic Peptide Design
by Yi Lu, Baomei Zhang, Zishuo Wang, Yidi He, Hezi Ge, Hongyue Ma and Pengfei Cui
Mar. Drugs 2026, 24(2), 76; https://doi.org/10.3390/md24020076 - 12 Feb 2026
Viewed by 976
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 [...] Read more.
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. Full article
(This article belongs to the Section Marine Pharmacology)
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20 pages, 3553 KB  
Article
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 - 11 Feb 2026
Viewed by 538
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 [...] Read more.
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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20 pages, 1927 KB  
Review
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
Viewed by 599
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 [...] Read more.
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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6 pages, 165 KB  
Editorial
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
Viewed by 333
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")
21 pages, 3014 KB  
Article
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
Viewed by 360
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 [...] Read more.
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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15 pages, 958 KB  
Review
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
Viewed by 484
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 [...] Read more.
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. Full article
(This article belongs to the Section Biomaterials of Marine Origin)
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18 pages, 1108 KB  
Review
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
Viewed by 637
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 [...] Read more.
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. Full article
(This article belongs to the Section Marine Pharmacology)
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18 pages, 3979 KB  
Article
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
Viewed by 481
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 [...] Read more.
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 (13), along with seven known analogs (410), were isolated from the marine fungus Penicillium sp. HN20. The structures of compounds 13 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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22 pages, 7559 KB  
Article
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
Viewed by 1380
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 [...] Read more.
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. Full article
(This article belongs to the Section Marine Pharmacology)
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20 pages, 4625 KB  
Article
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
Viewed by 471
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 [...] Read more.
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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20 pages, 7089 KB  
Article
Analytical Framework to Navigate Microalgae-Based Product Development—Aligning Commercialization and Regulatory Pathways
by 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
Viewed by 1012
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue From Marine Natural Products to Marine Bioproducts)
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26 pages, 2330 KB  
Article
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
Viewed by 527
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 [...] Read more.
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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27 pages, 3933 KB  
Article
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
Viewed by 362
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 [...] Read more.
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
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18 pages, 12875 KB  
Article
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
Viewed by 391
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 [...] Read more.
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. Full article
(This article belongs to the Section Synthesis and Medicinal Chemistry of Marine Natural Products)
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17 pages, 2040 KB  
Article
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
Viewed by 1107
Abstract
Ten new epipolythiodioxopiperazine (ETP) alkaloids, named corallomycetellains A–J (110), 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 [...] Read more.
Ten new epipolythiodioxopiperazine (ETP) alkaloids, named corallomycetellains A–J (110), 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 12 represent the first two examples of aranotin-type ETPs possessing an aromatic indole moiety. Compounds 24 all featured a unique C2-methyl disulfide substituent, whereas compound 4 additionally possessed a C2′-oxomethyl group. In in vitro cytotoxicity assays, compounds 710, which contained αα′ polysulfide bridges, exhibited strong anticancer activity, with IC50 values ranging from 1.1 to 9.3 μM. Full article
(This article belongs to the Section Structural Studies on Marine Natural Products)
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31 pages, 3611 KB  
Review
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
Viewed by 1347
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Pharmacognostic Potential of Seaweed Extracts and Metabolites)
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25 pages, 3024 KB  
Article
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
Viewed by 1329
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Marine Polysaccharides-Based Biomaterials)
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17 pages, 1840 KB  
Article
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
Viewed by 559
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 [...] Read more.
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. Full article
(This article belongs to the Section Marine Pharmacology)
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21 pages, 4244 KB  
Article
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
Viewed by 817
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Bioactive Molecules from Extreme Environments III)
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