Search Results (482)

Breast cancer remains a major global health burden. Dactylospongia species have been explored for their cytotoxic potential. This study aims to evaluate the cytotoxic potential of compounds derived from the marine sponge Dactylospongia elegans. Dactylospongia elegans were collected from the Lembeh Strait, macerated using methanol, then partitioned to an ethyl acetate fraction. The cytotoxic activity of these fractions was assessed using MDA-MB-231 cells while toxicity testing was done using the BSLT. TLC was carried out to determine the groups of compounds, while LC-MS/MS was used to predict active compounds contained in the ethyl acetate fractions. In silico studies were conducted as preliminary studies to determine the antitumor mechanism. The ethyl acetate fraction and F4 subfraction of Dactylospongia elegans exhibited cytotoxicity toward MDA-MB-231 cells with IC₅₀ values of 15.72 and 41.76 µg/mL, respectively. The BSLT indicated the strongest toxicity belongs to the F6 subfraction (LC₅₀ = 32.831 µg/mL). TLC analysis confirmed the presence of major secondary metabolites as terpenoids, steroids, and alkaloids, then confirmed with LC-MS/MS including 5-epi-illimaquinone and calciferol. Molecular docking revealed that calciferol exhibited the strongest binding affinity toward tyrosine kinase and p53–MDM2 receptors, with binding energies of −10.13 and −10.28 kcal/mol, respectively. These findings suggest that Dactylospongia elegans contains bioactive constituents with potential anticancer activity, particularly against TNBC. Full article

Antarctic marine-derived fungi represent an underexplored reservoir of bioactive secondary metabolites shaped by extreme environmental pressures. In this study, nine fungal isolates obtained from Antarctic macroalgae, lichens, sponge tissue, and sediments were evaluated for their antimicrobial, anticancer, antibiofilm, and metabolomic profiles. Untargeted LC–MS/MS molecular networking (GNPS) revealed a chemically rich metabolome, dominated by alkaloids, followed by polyketides, meroterpenoids, and diketopiperazines, with Penicillium crustosum (A15A) emerging as a major biosynthetic contributor. The annotation of structurally diverse metabolites, including roquefortines, viridicatin derivatives, andrastins, and multiple diketopiperazines, highlights the metabolic plasticity of Antarctic fungi. Anticancer evaluation indicated cytotoxicity, with Aspergillus awamori (A30), Alternaria malorum (A36), and Cladosporium malorum (A38) displaying activity toward HCT 116 colorectal cancer cells at IC₅₀ ≥ 30 µg/mL. Extracts were screened against methicillin-resistant Staphylococcus aureus (MRSA, COL), methicillin-susceptible S. aureus (MSSA, NCTC8325 4), and Escherichia coli K12, revealing low to no activity against these pathogens. Six of the nine isolates exhibited strong antibiofilm activity without inhibiting planktonic bacterial growth, indicating selective biofilm inhibition against MSSA and meeting the criteria for clinical developmental “hits”. Biofilm inhibition ranged from 81.10% to 98.50%, with A15A showing the highest activity (98.50% at 250 µg/mL), followed by A36 (91.16% at 31.35 µg/mL). Botrytis sp. (A22A), P. chrysogenum (A7), Ulocladium microsporum (A24B), and A30 also demonstrated strong antibiofilm activity (81.10–85.89%). To our knowledge, this is the first report describing antibiofilm activity of Antarctic fungal extracts. Full article

Rare actinomycetes have emerged as important yet underexplored reservoirs for the discovery of novel bioactive compounds. Microbispora, a genus of rare actinomycetes, is widely distributed across diverse ecological niches, including terrestrial soils, marine-associated environments, plant-associated ecosystems, and insect-derived environments. To date, 81 secondary metabolites have been reported from this genus, encompassing quinones, chromones and chromanones, macrolides, other polyketides, alkaloids, peptides and diketopiperazines, and miscellaneous structural classes. These metabolites display antimicrobial, anticancer, neuroprotective, antiviral, plant growth-promoting, and enzyme inhibitory activities. Beyond systematically cataloging these compounds, this review provides an integrated analysis of their structure–activity relationships (SAR), biosynthetic origins, and biological significance. In addition, the biosynthetic potential of Microbispora is discussed based on reported genomic studies, highlighting the presence of numerous predicted and poorly characterized biosynthetic gene clusters. This review provides an integrative perspective on Microbispora as an underexplored but promising source of structurally diverse and bioactive natural products for drug discovery. Full article

Background/Objectives: Marine microorganism metabolites are structurally unique secondary metabolites possessing therapeutic potential. The current study aims to identify a novel ATPase regulator using a newly established bidirectional activity evaluation system to screen for microbial metabolites that inhibit the activities of Na⁺-K⁺-ATPase or Ca²⁺-Mg²⁺-ATPase. Methods: A total of 1258 marine microbial strains were isolated from sea mud in Zhoushan, Zhejiang. Results: The extract of strain ZSDH2536 exhibited Na⁺-K⁺ and Ca²⁺-Mg²⁺-ATPase inhibitory activity and was identified as Sirastachys pandanicola based on morphological and molecular phylogenetic analyses. The secondary metabolite was tentatively identified in the ZSDH2536 strain as a bisindole compound, and named Pandanicoline based on ¹H-NMR, ¹³C-NMR and high-resolution mass spectrometry analysis. The chemical formula of Pandanicoline is C₅₁H₆₈N₂O₁₀, with an isotopic mass of 868.4874 Da. The maximum inhibition rate of Pandanicoline on Na⁺-K⁺ and Ca²⁺-Mg²⁺-ATPase was 36.37% and 37.27%, respectively. Moreover, in silico analysis also showed the binding energy of Pandanicoline with Na⁺-K⁺-ATPase was −9.124 kcal/mol and with the Ca²⁺-Mg²⁺-ATPase complex was −10.47 kcal/mol. Conclusions: The strain ZSDH2536 represents a promising source of dual inhibitors targeting Na⁺-K⁺ and Ca²⁺-Mg²⁺-ATPase. Pandanicoline exhibits potential as a lead compound for regulating ion homeostasis, providing new opportunities for further investigation into its mechanism and therapeutic applications. Full article

Four novel alkaloids, including three γ-lactam alkaloids (1–3) and one diketopiperazine (4), along with eight previously known compounds (5–12), were isolated from the marine-derived fungus Aspergillus fumigatus SYPHU504. Their structures, including the tentative stereochemical assignments of the side-chain double bonds in 2 and 3, were elucidated through comprehensive spectroscopic analysis and in comparison with the literature’s data. All isolated compounds were evaluated for their anti-leukaemic activities against human leukaemia cell lines K562 and RS4;11 using the MTT assay. Compounds 4, 6, 7, and 9–12 exhibited notable cytotoxic activities against both RS4;11 and K562 cell lines, with IC₅₀ values ranging from 5.02 ± 2.33 to 31.85 ± 0.50 μM. The results of Western blotting and Annexin V-FITC/PI staining elucidated that compounds 4, 7, and 10 could induce apoptosis in both RS4;11 cells and K562 cells. Full article

Manzamine-A (MA), a complex β-carboline alkaloid isolated from various genera of marine sponges, has attracted significant attention due to its unique structure and broad spectrum of potent biological activities. Despite the therapeutic potential, its development is limited by challenging natural supply and suboptimal pharmacokinetics. To address these barriers, innovative total syntheses of its intricate polycyclic framework have been achieved, enabling the development of semi-synthetic and synthetic analogues aimed at improving potency and drug-like properties. This review comprehensively outlines the progress in understanding this marine natural product, mainly focusing on its microbial origin, biological activities, pharmacokinetic behavior, chemical synthesis, and derivatives’ and analogues’ development. By integrating these diverse yet interconnected fields of research, this review bridges the critical gap between the natural product’s discovery and its clinical translation. Additionally, it also provides a roadmap for future drug development, highlighting how interdisciplinary collaboration can unlock the therapeutic potential of MA as a viable clinical candidate. Full article

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer activity, and preliminary structure–activity relationships. We found that sponges and marine-derived fungi are the most abundant sources of highly active compounds. Furthermore, knowledge graph-based analysis reveals that oxygen- and nitrogen-containing heterocycles constitute the core pharmacophores, and target prediction further indicates that MNPs exert anticancer effects through coordinated modulation of a multi-target network involving kinases, proteasomes, and nuclear receptors. This review contributes significantly to a deeper understanding of recent advances (2020–2024) in MNPs and provides critical guidance for promoting the development of innovative anticancer drugs derived from marine resources. Full article

This review paper covers publications from 2013 to July 2025, and describes brominated and non-brominated indole alkaloids, ircinianins, terpenoids, and polyketide compound classes from the marine sponge of the genus Psammocinia. It provides an overview of the reported secondary metabolites, their source organisms, geographic origins, and associated biological activities. Also, the structure-activity relationship study and biosynthetic pathways of the reported compounds are illustrated. Herein, 15 new secondary metabolites, including 11 terpenoids and four akaloids, were identified in the Psammocinia sponge species during this period. Briefly, the biological activities of these secondary metabolites involve molecular, cellular, and microbial targets. Full article

Triple-negative breast cancer represents one of the most aggressive and therapeutically challenging subtypes of breast malignancies, characterized by marked biological heterogeneity, rapid progression, and limited targeted treatment options. Conventional therapies are frequently constrained by drug resistance, systemic toxicity, and high rates of recurrence. In this context, natural products have gained increasing attention as multifunctional agents capable of modulating several hallmarks of triple-negative breast cancer. Bioactive compounds, including polyphenols, terpenoids, alkaloids, and marine-derived molecules, exhibit pleiotropic antitumor effects by interfering with key oncogenic pathways. Importantly, these compounds have demonstrated the ability to counteract major mechanisms of therapeutic resistance, modulate the tumor immune microenvironment, and enhance the efficacy of standard chemotherapy and immunotherapy. Advances in drug delivery strategies, such as nanoparticle-based systems and tumor-targeted formulations, together with patient-specific molecular profiling, further expand the potential of these agents within personalized treatment approaches. This narrative review critically examines the role of natural compounds in targeting the hallmarks of triple-negative breast cancer and their potential synergistic use to improve therapeutic efficacy while reducing treatment-related toxicity. Overall, the integration of natural product-based strategies into precision oncology frameworks may offer more effective, less toxic, and individualized therapeutic options for this aggressive breast cancer subtype. Full article

Plant-based biomaterials are increasingly recognized as bio-instructive platforms capable of actively modulating immune responses rather than functioning solely as passive structural supports. In this context, the term plant-based refers to photosynthetic biomass-derived platforms, including both terrestrial plants and marine macroalgae, reflecting their shared richness in polysaccharides and secondary metabolites relevant to immune engineering and regenerative medicine. This review critically synthesizes current evidence on plant-derived polysaccharides and phytochemicals, including algal sulfated polysaccharides (fucoidan, alginate, carrageenan, and ulvan), terrestrial plant polysaccharides (e.g., Lycium barbarum and Aloe vera derivatives), polyphenols, and other secondary metabolites such as terpenoids and alkaloids, highlighting their roles as immunomodulators in biomedical contexts. Key mechanisms include macrophage polarization along an M1–M2 continuum, pattern recognition receptor engagement, redox and metabolic regulation, and crosstalk between innate and adaptive immunity, with emphasis on context-dependent signaling and structural heterogeneity. Material design parameters, including molecular weight and chemical functionalization, are critical determinants of immune responses. Advanced delivery systems, such as hydrogels, nanocomposites, phytosomes, and plant-derived extracellular vesicles (EVs), enable improved stability and spatiotemporal control. Applications in wound and musculoskeletal regeneration are discussed alongside translational challenges, including variability, reproducibility, regulatory issues, and the need for standardized characterization and immune validation. Full article

The cold-water siliceous sponge Geodia barretti, largely present in the North Atlantic Ocean, notably around Scandinavian costs, plays important roles in carbon and silicon cycling in the deep-sea. The demosponge provides a reservoir for numerous microorganisms. Bioactive natural products have been isolated from this sponge, in particular the indole alkaloid barettin discovered forty years ago. Barettin and analogues, notably 8,9-dihydrobarettin, 8,9-dihydro-8-hydroxybarrettin, bromobenzisoxalone barettin, and geobarrettins A-B, contribute to the maintenance of the sponge stability and security (anti-fouling) and the regulation of its microbial environment. The four indole alkaloids 6-bromo-8-hydroxyconicamin, 6-bromoconicamin, and geobarrettin C-D are also implicated in the defense of the sponge against physical and biochemical aggressions. Altogether, these ten natural products are essential to the sponge life. The present review presents a survey of the chemistry and biology associated with Geodia barretti. The pharmacological properties of (dihydro)barettin, notably their antioxidant and anti-inflammatory properties, are discussed, as well as the synthetic processes set up to produce these diketopiperazine derivatives. Their molecular targets and mechanism of action are also discussed. The review takes the sponge G. barretti from the depths of knowledge and brings barettin and analogues to the surface, with the hope of guiding future research in this field. Full article

Respiratory syncytial virus (RSV) poses a substantial global health burden, particularly in infants and the elderly. The fusion (F) protein is a key therapeutic target for inhibiting RSV entry. In this study, we performed a structure-based virtual screening of the Comprehensive Marine Natural Products Database (CMNPD) to discover novel anti-RSV agents targeting the prefusion F protein trimer. Screening of 31,561 compounds via molecular docking, followed by stringent ADMET (absorption, distribution, metabolism, excretion, and toxicity) profiling and MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) binding free energy calculations, identified 11 promising candidates. Among these, manzamine alkaloids exhibited the most favorable docking scores (as low as −13.3 kcal/mol) and promising Ligand Efficiency (LE) values. These molecules primarily interact with conserved hydrophobic residues (Phe140, Phe488) through hydrophobic interactions, π-stacking, and electrostatic forces. Our study highlights marine natural products, especially manzamine alkaloids, as promising leads for the development of novel, orally bioavailable RSV fusion inhibitors, potentially offering avenues to overcome existing drug resistance. However, these computational findings require in vitro validation to confirm efficacy. Full article

Autophagy is an evolutionarily preserved intracellular degradation process pivotal in maintaining proteostasis, mitochondrial homeostasis, and metabolic equilibrium, all of which are dysregulated with aging. Aberrant autophagy has been recognized as a hallmark of human aging and age-related diseases, including neurodegeneration, metabolic dysfunction, cardiovascular diseases, and cancer. Bioactive natural compounds derived from plants, foods, and marine organisms have emerged as potent modulators of autophagy, offering a promising strategy to counteract aging and promote healthy lifespan. Mechanistically, these compounds regulate autophagy by modulating key signaling pathways, such as AMPK, PI3K/AKT/mTOR, SIRT1, and FOXO, while also alleviating oxidative stress, inflammation, and mitochondrial dysfunction. Natural compounds like polyphenols, flavonoids, alkaloids, terpenoids, and carotenoids exhibit dual roles by restoring age-related suppressed autophagic flux and inhibiting excessive autophagy-induced cell death. In this review, we provide a comprehensive overview of the molecular mechanisms through which bioactive natural compounds modulate autophagy and impact human aging and longevity. We discuss both experimental and clinical evidence supporting their geroprotective effects, limitations regarding bioavailability and dose-dependent effects, and prospects for the utilization of autophagy-targeting natural products in aging intervention strategies. Full article

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

Background: Staurosporine is a potent broad-spectrum alkaloid antibiotic originally isolated from Streptomyces sp. It is renowned for its strong inhibitory activity against protein kinases by competitively binding to their ATP-binding sites. Therefore, staurosporine and its derivatives have been extensively investigated for their potential as anticancer agents. However, a major challenge in its utilization is the low production yield in wild-type strains. To overcome this limitation, this study aimed to enhance staurosporine yield in marine-derived staurosporine-producing strain OUCMDZ-3118. Methods: The fermentation conditions were tested by single-factor experiment, Plackett–Burman experiment, steepest ascent path and Box–Benhnken response surface method. Subsequently, the ultraviolet mutagenesis was employed to generate high-yielding mutant strain. Results: The optimal culture conditions were 50 g/L rice, 50 g/L soybean powder, 3 g/L NaCl, 10 g/L L-tryptophan, inoculum concentration of 3% (v/v) in 150 mL of medium within a 500 mL flask, and fermentation time of 10 days. Following UV mutagenesis, the mutant strain produced a final staurosporine titer of 496 mg/L, an approximately 9.5-fold higher titer than that of the wild-type strain. In a 30-day solid-state fermentation under the conditions of 40 g rice, 40 g soybean powder, moistened with 80 mL water containing NaCl (3 g/L) and L-tryptophan (10 g/L), a yield of 578 mg per 80 g of substrate was also achieved. A consistent yield of 7.22 g/kg was achieved across approximately 1000 replicate fermentations under identical conditions, demonstrating the robustness of the process. Conclusions: This study yielded a stable, high-yielding strain for staurosporine production, paving the way for the development of staurosporine-based antitumor drugs and their derivatives. Full article