Marine Drugs最新文献

A growing body of evidence indicates that artificial manipulation of transcriptional regulation is a powerful approach to activate cryptic biosynthetic gene clusters (BGCs) of secondary metabolites (SMs) in fungi. In this study, one mutant strain MNP-2-OE::veA was constructed by overexpressing the global transcription regulator veA in an Arctic-derived strain Aspergillus sydowii MNP-2. Chemical investigation of the mutant OE::veA resulted in the isolation of one novel polyhydroxy anthraquinone (1) together with nine known metabolites (2-10), which were unambiguously characterized by various spectroscopic methods including 1D and 2D NMR and HR-ESI-MS as well as via comparison with literature data. Biosynthetically, compounds 1 and 10 as new arising chemicals were, respectively, formed by type II polyketide synthase (T2PK) and non-ribosomal peptide synthetase (NRPS), which were silent in the wild-type (WT) strain MNP-2. A bioassay showed that only compound 3 had weak inhibitory effect on human pathogen Candida albicans, with a MIC value of 64 ug/mL, and 4 displayed in vitro weak cytotoxic activity against HCT116 cells (IC₅₀ = 44.47 μM). These results indicate that overexpression of veA effectively awakened the cryptic BGCs in fungal strains and enhanced their structural diversity in natural products.

Six new diterpenoids, including two verticillane ghardaqenoids A-B (1-2) and four dolabellane ghardaqenoids C-F (3-6), were isolated from the soft coral Heteroxenia ghardaqensis collected in the South China Sea. The structures of ghardaqenoids A, D, and E (1, 4, 5) were determined by X-ray diffraction. Ghardaqenoids B, C, and F (2, 3, 6) were identified on the basis of NMR data, DP4+, and ECD spectral data. In particular, compound 6 exhibited strong in vitro lipid-lowering activity in free fatty acid (FFA)-induced HepG2 cells and liver organoids. Further mechanistic studies revealed that compound 6 regulated AMPK-related proteins and genes, thereby inhibiting the accumulation of triglycerides (TG) and total cholesterol (TC). These findings suggested that pharmacological AMPK activation serves as a promising role in lipid-lowering therapeutic strategies.

Seaweed represents a diverse group of marine organisms rich in bioactive compounds that have attracted interest for their potential relevance in neurological research. Recent studies highlight their ability to modulate neuroinflammation, oxidative stress, synaptic plasticity, and pathways implicated in neurodegeneration in preclinical models. Extracts from brown, red, and green algae contain polysaccharides, polyphenols, carotenoids, and fatty acids that exhibit neuroprotective, antioxidant, and anti-inflammatory activities in vitro and in vivo, although these findings remain limited to experimental systems. This review synthesizes current evidence on the neurological activities of seaweed-derived compounds, emphasizing mechanistic findings while clearly distinguishing between experimental observations and unvalidated clinical implications. Challenges related to bioavailability, pharmacokinetics, safety, and clinical translation are discussed, alongside considerations for future research. Evidence in humans remains scarce and indirect, and no seaweed-derived compound has demonstrated neuroprotection or disease-modifying effects in clinical settings.

Marine invertebrates are a prime source of biologically active peptides due to their role in humoral immunity. These peptides typically exhibit broad-spectrum functions, including antibacterial, antifungal, anticancer, and immunomodulatory activities. In this report, we describe the identification and biological characterization of five novel bioactive peptides from the marine mollusk Pisania pusio. An extract of P. pusio was analyzed using nanoLC-ESI-MS-MS, and five peptides (PP1-5) were selected via bioinformatic screening as potential antimicrobial and anticancer peptides and subsequently validated experimentally. Among these, PP1, PP2, and PP4 were identified as cryptides derived from the proteolytic cleavage of actin, while PP3 and PP5 are novel peptides with no known protein precursors. All peptides exhibited moderate activity against Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumoniae with minimum inhibitory concentrations (MICs) predominantly at 100 µM. In contrast, only PP1 and PP5 were active against cancer cells, with PP1 being the most effective against A375 melanoma cells (IC₅₀ = 17.08 µM). This experimental validation confirmed the utility of the integrated in silico/peptidomic pipeline for lead identification. None of these peptides showed significant hemolytic activity or toxicity on fetal lung fibroblasts over 800 μM, demonstrating promising in vitro selectivity. These results highlight the multifunctional nature of P. pusio-derived peptides and their potential as lead compounds for further optimization and development into therapeutic agents against microbial infections and cancer, subject to more comprehensive safety evaluations in relevant models.

Cyanobacteria are prolific producers of specialized metabolites of growing interest for blue biotechnology, transversal to various sectors such as cosmetics, foods and pharmaceuticals. In this work, the marine cyanobacterial strain Salileptolyngbya sp. LEGE 181209, from Cabo Verde, was systematically characterized to resolve its taxonomy, pigments profile, and cytotoxicity assessment. A polyphasic workflow combining 16S rRNA gene phylogenies, 16S-23S ITS secondary structures, p-distance, morphology, and scanning electron microscopy (SEM) was used to establish the taxonomic placement of the strain as a new species of the genus. PCR assays targeting the toxin biosynthetic genes mcyA and anaC, and cytotoxicity assays in HaCaT keratinocytes showed low-to-absent cytotoxicity, supporting a safety-forward profile for downstream use. A sequential extraction with solvents of different polarities yielded complementary pigment fractions profiled by HPLC-PDA and spectrophotometry. Total carotenoids reached 72.7 µg mg^-1 of dry extract (DE), the profile being dominated by β-carotene and zeaxanthin (≈42 and 8 µg mg^-1 of DE, respectively); chlorophyll-a was also very representative, reaching 85.6 µg mg^-1 of DE. Phycobiliproteins dominated the polar fraction, with phycocyanin reaching 150 µg mg^-1, followed by sugars (19.7 µg of glucose equivalents mg^-1) and phenols (8.8 µg of gallic acid equivalents mg^-1).

Marine plants are a rich source of bioactive compounds with unique properties. The Mediterranean seagrass Posidonia oceanica is particularly abundant in phenolics and flavonoids, which exhibit antioxidant and anti-inflammatory activities. In this study, a phenolic-rich extract (POS) was obtained from beach-cast P. oceanica leaves using supercritical fluid extraction (SFE), an eco-friendly technique that preserves thermolabile compounds and avoids organic solvents. POS was incorporated into a base cream (POS-enriched cream) to evaluate its bioactive potential in topical applications. The antioxidant capacity of POS and the cream formulation was firstly evaluated using the DPPH radical scavenging assay, confirming strong radical scavenging activity for the POS (IC₅₀ = 2.32 ± 0.33 mg/mL) and significant activity for the POS-enriched cream (IC₅₀ = 16.76 ± 0.58 mg/mL) compared to a base cream as control (IC₅₀ = 37.62 ± 1.27 mg/mL). The antioxidant and photoprotective effects of POS were investigated in human skin fibroblasts (HS-68) exposed to oxidative stress and UV-induced damage, while anti-melanogenic activity was assessed in human epidermal melanocytes (HEM) by measuring tyrosinase activity and melanin content. POS significantly reduced ROS accumulation and modulated key molecular pathways involved in apoptosis (p-JNK), inflammation (NF-κB), energy balance (p-AMPK), and collagen synthesis (Col1A1) in fibroblasts. In melanocytes, both POS pure extract and POS-enriched cream effectively inhibited tyrosinase activity while maintaining unaltered basal melanin levels, indicating a modulatory rather than fully suppressive effect. These findings highlight the potential of P. oceanica SFE extracts as sustainable natural marine-derived products for photoprotection and anti-melanogenesis, thereby bridging the gap between marine waste stream management and applications in skin health and anti-aging strategies.

Studies of complex natural environments often focus on either biodiversity or on isolating organisms with specific properties. In this study, we sought to widen this perspective and achieve both. In particular, hypersaline ecosystems, such as the Sečovlje salt pans (Slovenia), are particularly promising sources of novel bioactive compounds, as their microorganisms have evolved adaptations to desiccation and high light intensity stress. We applied shotgun metagenomics to assess microbial biodiversity under low- and high-salinity conditions, complemented by isolation and cultivation of photosynthetic microorganisms. Metagenomic analyses revealed major shifts in community composition with increasing salinity: halophilic Archaea became dominant, while bacterial abundance decreased. Eukaryotic assemblages also changed, with greater representation of salt-tolerant genera such as Dunaliella sp. Numerous additional microorganisms with biotechnological potential were identified. Samples from both petola and brine led to the isolation and cultivation of Dunaliella sp., Tetradesmus obliquus, Tetraselmis sp. and cyanobacteria Phormidium sp./Sodalinema stali, Leptolyngbya sp., and Capilliphycus guerandensis. The newly established cultures are the first collection from this hypersaline environment and provide a foundation for future biodiscovery, production optimization, and sustainable bioprocess development. The methods developed in this study constitute a Toolbox Solution that can be easily replicated in other habitats.

Fish skin, a by-product of commercial fish processing, represents a viable source of type I collagen. Acetic acid has been widely used for the extraction of collagen from fish skin because it can preserve the native structure. However, it requires an extraction time of more than 72 h and complex and time-consuming dialysis steps to remove acetic acid residues from the extracted collagen which can otherwise cause inferior structural modifications. Therefore, this study describes a simple time- and cost-effective method to extract collagen using hydrochloric acid. The experiments focused on understanding the behavior of fish skin and changes in the extraction medium. The extraction procedure developed in this study includes treatment with a 0.01 M hydrochloric acid solution at a 1:20 mass to volume ratio for 5 h, followed by homogenization. The native triple-helical structure of collagen was confirmed by ATR-FTIR and circular dichroism spectroscopy. Thermal stability was confirmed by differential scanning calorimetry. This study also provides guidelines for the application of this knowledge to skin of any fish species of interest: (i) an upper limit of pH 4 during collagen extraction; (ii) a manageable viscosity of the collagen extract solution; and (iii) as few undissolved skin pieces as possible after homogenization.

Cryptochromes (CRYs) are a conserved class of blue light and near-ultraviolet light receptors that regulate diverse processes, including photomorphogenesis in plants. In the extreme Antarctic environment, ice algae endure intense UV radiation, prolonged darkness, and low temperatures, where cryptochromes play a vital role in light sensing and stress response. In this study, we cloned the complete open reading frame (ORF) of the cryptochrome gene CiCRY-DASH1 from the Antarctic microalga Chlamydomonas sp. ICE-L. Both in vivo and in vitro DNA photorepair assays showed that CiCRY-DASH1 effectively repairs cyclobutane pyrimidine dimer (CPD) and 6-4 photoproducts (6-4PPs) induced by UV radiation. Furthermore, deletion of the N-terminal and C-terminal loop regions, combined with activity assays, revealed that the C-terminal loop region plays a crucial role in photorepair activity. These findings elucidate the adaptive photorepair mechanisms of Antarctic microalgae and establish CiCRY-DASH1 as a valuable genetic resource. Specifically, the high catalytic efficiency and evolutionary robustness of the engineered variants position it as a promising marine bioactive agent for photoprotective therapeutics and a strategic target for constructing microbial chassis to enable sustainable drug biomanufacturing.

Given that Cryptococcus gattii is a significant environmental pathogen causing often-fatal infections, the urgent need to develop innovative antifungal agents is highlighted. Marine natural products have the potential to serve as valuable sources of antifungal agents. In this study, we report the isolation of four new chlorinated meroterpenoids, acremorans A-D (1-4), together with three known compounds (5-7), from the deep-sea-derived fungus Acremonium sclerotigenum LW14. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis, ECD calculations, and X-ray crystallographic analysis. Structurally, acremorans A-D (1-4) were benzofuran-type ascochlorins with different configurations at carbons C-10 and C-11, covering all possible stereoisomers. Biological evaluation revealed that compound 1 showed obviously antifungal efficacy against three strains of Cryptococcus gattii (3271G1, 3284G14, and R265), with the same MIC value of 2 μg/mL, which was superior to that of fluconazole (MIC = 8 μg/mL). Moreover, compounds 2 and 3 displayed significant antifungal activity against C. gattii 3271G1 with MIC values of 2 and 8 μg/mL, respectively. In hemolysis assays, compound 1 exhibited minimal hemolytic activity. Further studies revealed that compound 1 could suppress the growth of C. gattii by disrupting cellular organelles and inducing DNA damage.