Search Results (1,228)

Marine natural products have gained increasing interest in drug research and development because of their unique structures, diverse biological activities, and novel mechanisms of action. Using the antiviral alkaloid aldisine as the lead compound and utilizing the hydrogen bond effects common in drug design, novel derivatives containing an acylhydrazone moiety were designed and synthesized. The structures of these derivatives were systematically analyzed using variable-temperature ¹H-NMR. Antiviral activity tests showed that most derivatives were active against tobacco mosaic virus (TMV), with some compounds outperforming the commercial antiviral drug ribavirin. Notably, 3-methylphenyl- and 3-pyridyl-substituted acylhydrazones 5-6 and 5-12 displayed activity comparable to ningnanmycin, one of the most effective commercial antiviral agents. Molecular docking results indicated that incorporating the acylhydrazone moiety enhances hydrogen bonding between the molecules and target proteins. Additionally, we evaluated the fungicidal and larvicidal activities of these derivatives. Most exhibited significant larvicidal effects against Mythimna separata and Plutella xylostella, along with broad-spectrum fungicidal activity. Four related compounds (5-11, 5-12, 5-13, and 5-17) exhibited high fungicidal activities, and another four compounds (2-4, 5-6, 5-13, and 5-17) exhibited high larvicidal activities. Full article

Oxidative stress caused by excessive reactive oxygen species (ROS) contributes to numerous chronic diseases. Marine green algae of the Caulerpa genus are rich in bioactive compounds with potential antioxidant activity. Objective: This study aimed to evaluate the intracellular antioxidant effects of caulerpin (CAU) and its derivative caulerpinic acid (CA) using Saccharomyces cerevisiae as a eukaryotic model. Methods: Yeast cells were pretreated with 1 μM of CAU or CA, or with 1 μM of resveratrol (RESV) as a positive control, then exposed to 2 mM of H₂O₂. Growth, ROS levels, oxidative damage markers, and antioxidant defenses were assessed. Results: Both CAU and CA significantly improved cell survival under oxidative stress, restoring growth rates (CAU: 0.129 h⁻¹, CA: 0.137 h⁻¹) and doubling times (CAU: 5.38 h, CA: 5.07 h) close to control values. Intracellular ROS accumulation, protein carbonylation, and lipid peroxidation were reduced to near-baseline levels. While catalase (Cat) and superoxide dismutase (Sod) activity remained unchanged, CAU and CA elevated intracellular glutathione (GSH) levels (1.6–1.8 fold) and preserved glutathione peroxidase (GPx) activity, compared to stressed cells without antioxidant pretreatment. Conclusions: CAU and CA act as effective intracellular antioxidants, primarily via ROS scavenging and GSH-dependent pathways. These findings support their potential as natural candidates for developing antioxidant-based therapies against ROS-related disorders. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, driven by dyslipidemia, chronic inflammation, oxidative stress, and endothelial dysfunction. Despite widespread use of lipid-lowering and anti-inflammatory agents such as statins, residual cardiovascular risk and adverse effects underscore the need for novel, safe, and multi-targeted therapies. Marine-derived polysaccharides (MDPs)—including fucoidan, alginate, laminarin, carrageenan, and chitosan—exhibit a spectrum of bioactivities relevant to ASCVD pathogenesis, such as anti-inflammatory, antioxidant, lipid-modulatory, antithrombotic, and endothelial-protective effects. In this critical review, we synthesize preclinical and emerging clinical evidence on the pharmacokinetics, mechanisms of action, and therapeutic potential of these compounds. We highlight translational challenges, including structural variability, poor oral bioavailability, and limited human data, and propose strategies to overcome these barriers, such as molecular standardization, novel delivery systems, and well-designed clinical trials. MDPs represent promising natural therapeutics for ASCVD prevention and treatment, warranting further investigation in rigorous human studies. Full article

The widespread emergence of resistant pathogenic microorganisms are diminishing the effectiveness of existing antimicrobial drugs, posing an enormous threat to global public health. This phenomenon, known as antimicrobial resistance (AMR), is primarily driven by the misuse and overuse of antimicrobial drugs. Natural product researchers around the globe, in response to antibiotics resistance, are searching for new antimicrobial lead compounds from unexplored or underexplored ecological niches such as the marine environment. In order to isolate new antimicrobial lead compounds, two Streptomyces spp. were isolated from marine sediment samples by a serial dilution technique and subsequently cultured in modified Bennett’s broth medium. Repeated chromatographic steps of ethyl acetate (EtOAc) extracts obtained from the culture broth led to the isolation of a new compound with an unusual chemical skeleton, streptopiperithiazol (1), and a synthetically known (2) compound. These compounds were characterized by the extensive analysis of 1D and 2D spectroscopic as well as HRMS data. The absolute configuration of 1 was unresolved due to limited yield and lack of proper facilities for taking CD and ECD spectra. In vitro activity study of compounds 1 and 2 revealed that these compounds had better activity against Gram-positive bacteria than Gram-negative bacteria and yeast. Full article

Macroalgae are valuable natural sources for bioprospection and the development of raw materials applicable to the nutrition, health, and agriculture industries. To build a basis for the sustainable use of marine organisms from the Colombian Caribbean, a preliminary study was conducted focusing on known functional compounds in two genera of macroalgae, including the species Acanthophora spicifera (Rhodophyta), Sargassum ramifolium, and Sargassum fluitans (Ochrophyta). This study included the extraction and identification of polysaccharides using ultrafiltration, nuclear magnetic resonance (¹H-NMR), Fourier-transform infrared spectroscopy (FT-IR), and size exclusion chromatography (SEC); fatty acids by gas chromatographic (GC) profiling; and phenolic composition and antioxidant activity by complementary semi-quantitative methods (ABTS, DPPH, FRAP, and ORAC assays). Carrageenan-type polysaccharides were detected in A. spicifera, while alginate and fucoidan types were found in S. ramifolium and S. fluitans; palmitic acid was the predominant fatty acid in A. spicifera and S. ramifolium, but it was not detected in S. fluitans. S. ramifolium showed the highest ABTS, DPPH, and ORAC activities and phenolic compounds, while S. fluitans exhibited the highest FRAP activity. This study contributes to the chemical knowledge on Colombian macroalgae to establish potential applications in various fields, including biomedicine, cosmetics, functional foods, and nutraceutical ingredients. Full article

In recent decades, there has been a marked surge in the development of marine-by-product-derived ingredients for cosmetic applications, driven by the increasing demand for natural, sustainable, and high-performance formulations. Marine animal by-products, particularly those from fish, crustaceans, and mollusks, represent an abundant yet underutilized source of bioactive compounds with notable potential in cosmeceutical innovation. Generated as waste from the fishery and seafood-processing industries, these materials are rich in valuable bioactives, such as chitosan, collagen, peptides, amino acids, fatty acids, polar lipids, lipid-soluble vitamins, carotenoids, pigments, phenolics, and mineral-based substrates like hydroxyapatite. Marine by-product bioactives can be isolated via several extraction methods, and most importantly, green ones. These compounds exhibit a broad spectrum of skin-health-promoting effects, including antioxidant, anti-aging, anti-inflammatory, antitumor, anti-wrinkle, anti-hyperpigmentation, and wound-healing properties. Moreover, applications extend beyond skincare to include hair, nail, and oral care. The present review provides a comprehensive analysis of bioactives obtained from marine mollusks, crustaceans, and fish by-products, emphasizing modern extraction technologies with a focus on green and sustainable approaches. It further explores their mechanisms of action and documented efficacy in cosmetic formulations. Finally, the review outlines current limitations and offers future perspectives for the industrial valorization of marine by-products in functional and environmentally-conscious cosmetic development. Full article

The marine seaweed Undaria pinnatifida belongs to the large group of brown macroalgae (Ochrophyta) and is valued both as a nutritious food and a source of pharmaceutical compounds. It has been widely consumed in East Asia as part of the traditional diet and is generally regarded as a “healthy longevity food.” Consequently, it represents one of the most promising natural sources of biomedicinal and bioactive products. This review aims to synthesize current scientific evidence on the pharmacologically active compounds of U. pinnatifida, emphasizing their mechanisms of action and therapeutic potential in neurodegenerative and chronic diseases. This narrative review is based on a comprehensive literature search of peer-reviewed articles from scientific databases, focusing on studies addressing the pharmacological properties of U. pinnatifida and its major bioactive constituents. Recent research highlights that compounds such as fucoxanthin (a carotenoid), fucosterol (a sterol), fucoidan (a polysaccharide), alginate, and dietary fiber found in U. pinnatifida possess significant potential for developing treatments for conditions including goitre, urinary diseases, scrofula, dropsy, stomach ailments, and hemorrhoids. Moreover, these compounds exhibit remarkable pharmacological properties, including immunomodulation, antitumor, antiviral, antioxidant, antidiabetic, anti-inflammatory, anticoagulant, antithrombotic, and antibacterial activities, all with low toxicity and minimal side effects. Additionally, U. pinnatifida shows promise in the treatment or prevention of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, as well as neuropsychiatric conditions like depression, supported by its antioxidant effects against oxidative stress and neuroprotective activities. Numerous in vitro and in vivo studies have confirmed that U. pinnatifida polysaccharides (UPPs), particularly fucoidans, exhibit significant biological activities. Thus, accumulating evidence positions UPPs as promising therapeutic agents for a variety of diseases. Full article

Alzheimer’s disease (AD) is a prevalent neurodegenerative disorder with a pressing need for novel therapeutics. However, current medications only offer symptomatic relief, without tackling the underlying pathology. To explore the bioactive potential of marine-derived fungi, this study focused on Aspergillus terreus C23-3, a strain isolated from the coral Pavona cactus in Xuwen County, China, which showed a richer metabolite fingerprint among the three deposited A. terreus strains. AntiSMASH analysis based on complete genome sequencing predicted 68 biosynthetic gene clusters (BGCs) with 7 BGCs synthesizing compounds reported to have anti-AD potential, including benzodiazepines, benzaldehydes, butenolides, and lovastatin. Liquid chromatography coupled with mass spectrometry (LC-MS)-based combinational metabolomic annotation verified most of the compounds predicted by BGCs with the acetylcholinesterase (AChE) inhibitor territrem B characterized from its fermentation extract. Subsequently, molecular docking showed that these compounds, especially aspulvione B1, possessed strong interactions with AD-related targets including AChE, cyclin-dependent kinase 5-p25 complex (CDK5/p25), glycogen synthase kinase-3β (GSK-3β), and monoamine oxidase-B (MAO-B). In conclusion, the genomic–metabolomic analyses and molecular docking indicated that C23-3 is a high-value source strain for anti-AD natural compounds. Full article

Background: 1,2,3,4,5-pentathiepines (PTEs) are compounds originally identified in marine ascidians and are currently under investigation for their promising pharmacological properties, particularly as potential antineoplastic agents. Objectives: In this study, we investigated the antineoplastic properties of a series of ten indolizine-based PTEs, comprising eight previously reported compounds and two newly synthesized derivatives. Methods: These compounds were evaluated against a panel of human cancer cell lines of diverse tissue origins, as well as, for the first time, on non-cancerous CR9 fibroblasts to assess their cytotoxic selectivity. In addition, their effects were tested on 3D spheroid models, providing preliminary insights into their potential in vivo efficacy. Initial screening focused on cell viability, followed by a more detailed characterization of the most active compounds in terms of their ability to induce apoptosis, necrosis, cell cycle arrest, and reactive oxygen species (ROS) generation. The anti-migratory activity of PTEs and a newly adapted assay to confirm sulfur species release in the cells were also performed for the first time. Results and Conclusions: Our findings reveal that four PTEs bearing hydrophilic, hydrogen-bonding functional groups, particularly the two inspired by natural analogs, exhibited the most potent anticancer activity. Full article

As the global demand for eco-friendly food ingredients grows, marine macroalgae emerge as a valuable resource for multiple applications using a circular bioeconomy approach. In this study, green macroalgae Ulva flexuosa, naturally accumulated in aquaculture ponds as a residual biomass (by-product) of shrimp and oyster farming, were investigated regarding their bioactivity, chemical composition, and antioxidant properties. The use of aquaculture by-products as raw materials not only reduces waste accumulation but also makes better use of natural resources and adds value to underutilized biomass, contributing to sustainable production systems. For this, a comprehensive approach including the evaluation of its composition and environmentally friendly extraction of bioactive compounds was conducted and discussed. Green macroalgae exhibited high fiber (37.63% dry weight, DW) and mineral (30.45% DW) contents. Among the identified compounds, palmitic acid and linoleic acid (ω-6) were identified in the highest concentrations. Pigment analysis revealed a high concentration of chlorophylls (73.95 mg/g) and carotenoids (17.75 mg/g). To evaluate the bioactivity of Ulva flexuosa, ultrasound-assisted solid–liquid extraction was performed using water, ethanol, and methanol. Methanolic extracts showed the highest flavonoid content (59.33 mg QE/100 g), while aqueous extracts had the highest total phenolic content (41.50 mg GAE/100 g). Ethanolic and methanolic extracts had the most potent DPPH scavenging activity, whereas aqueous and ethanolic extracts performed best at the ABTS assay. Overall, we show the upcycling of Ulva flexuosa, an underexplored aquaculture by-product, as a sustainable and sensible strategy for multiple value-added applications. Full article

The Arabian Gulf, bordered by major energy-producing nations, harbors diverse microalgal communities with strong potential for the bioremediation of environmental pollutants, particularly petroleum hydrocarbons. This review evaluates two key microalgal groups—micro-green algae and dinoflagellates—highlighting their distinct physiological traits and ecological roles in pollution mitigation. Dinoflagellates, including Prorocentrum and Protoperidinium, have demonstrated hydrocarbon-degrading abilities but are frequently linked to harmful algal blooms (HABs), marine toxins, and bioluminescence, posing ecological and health risks. The toxins produced by these algae can be hemolytic or neurotoxic and include compounds such as azaspiracids, brevetoxins, ciguatoxins, okadaic acid, saxitoxins, and yessotoxins. In contrast, micro-green algae such as Oedogonium and Pandorina are generally non-toxic, seldom associated with HABs, and typically found in clean freshwater and brackish environments. Some species, like Chlorogonium, indicate pollution tolerance, while Dunaliella has shown promise in remediating contaminated seawater. Both groups exhibit unique enzymatic pathways and metabolic mechanisms for degrading hydrocarbons and remediating heavy metals. Due to their respective phycoremediation capacities and environmental adaptability, these algae offer sustainable, nature-based solutions for pollution control in coastal, estuarine, and inland freshwater systems, particularly in mainland Qatar. This review compares their remediation efficacy, ecological impacts, and practical limitations to support the selection of effective algal candidates for eco-friendly strategies targeting petroleum-contaminated marine environments. Full article

Tuberculosis (TB) poses a persistent global health threat exacerbated by the emergence of drug-resistant strains; hence, there is a continuous quest for novel antimicrobial agents. Despite efforts to develop effective therapies, existing treatments require a relatively long duration of therapy to eradicate the pathogen due to its virulence factors, pathogenesis patterns, and ability to enter dormant states. This can lead to a higher risk of treatment failure due to poor patient adherence to the complex regimen. As a result, considerable research is necessary to identify alternative antituberculosis agents. The marine environment, particularly marine-derived fungi, has recently gained interest due to its potential as an abundant source of bioactive natural products. This review covers 19 genera of marine-derived fungi and 139 metabolites, 131 of which exhibit antimycobacterial activity. The integrated dataset pinpoints the fungal genera and chemical classes that most frequently yield potent antimycobacterial hits while simultaneously exposing critical gaps, such as the minimal evaluation of compounds against dormant bacilli and the presence of underexplored ecological niches and fungal genera. Several compounds exhibit potent activity through uncommon mechanisms, including the inhibition of mycobacterial protein tyrosine phosphatases (MptpB/MptpA), protein kinase PknG, ATP synthase and the disruption of mycobacterial DNA via G-quadruplex stabilization. Structure–activity relationship (SAR) trends are highlighted for the most potent agents, illuminating how specific functional groups underpin target engagement and potency. This review also briefly proposes a dereplication strategy and approaches for toxicity mitigation in the exploration of marine-derived fungi’s natural products. Through this analysis, we offer insights into the potency and challenges of marine-derived fungi’s natural products as hit compounds or scaffolds for further antimycobacterial research. Full article

A recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge Agelas axifera with in vitro activity against an economically important parasitic nematode, Haemonchus contortus (barber’s pole worm). The bioassay-guided fractionation of the CH₂Cl₂/MeOH extract from A. axifera led to the purification of a new diterpene alkaloid, agelasine Z (1), together with two known compounds agelasine B (2) and oxoagelasine B (3). Brominated compounds (–)-mukanadin C (4) and 4-bromopyrrole-2-carboxylic acid (5) were also isolated from neighbouring UV-active fractions. All compounds, together with agelasine D (6) from NatureBank’s pure compound library, were tested for in vitro anthelmintic activity against exsheathed third-stage (xL3s) and fourth-stage larvae (L4s) of H. contortus and young adult Caenorhabditis elegans. Compounds 1, 2 and 6 induced an abnormal “skinny” phenotype, while compounds 2 and 6 also reduced the motility of H. contortus L4s by 50.5% and 51.8% at 100 µM, respectively. The minimal activity of agelasines against C. elegans young adults suggests a possible species-specific mechanism warranting further investigation. For the first time, the unexpected lability of agelasine H-8′ was explored using kinetic studies, revealing rapid deuterium exchange in MeOH-d₄ at room temperature. Full article

Chronic pain affects approximately 20% of the global adult population, posing significant healthcare and economic challenges. Effective management requires addressing both biological and psychosocial factors, with emerging therapies such as antioxidants and marine algae offering promising new treatment avenues. Marine algae synthesize bioactive compounds, including polyphenols, carotenoids, and sulfated polysaccharides, which modulate oxidative stress, inflammation, and neuroimmune signaling pathways implicated in pain. Both preclinical and clinical studies support their potential application in treating inflammatory, neuropathic, muscular, and chronic pain conditions. Notable constituents include polyphenols, carotenoids (such as fucoxanthin), vitamins, minerals, and sulfated polysaccharides. These compounds modulate oxidative stress and inflammatory pathways, particularly by reducing reactive oxygen species (ROS) and downregulating cytokines such as tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). Brown and red algae produce phlorotannins and fucoidans that alleviate pain and inflammation in preclinical models. Carotenoids like fucoxanthin demonstrate neuroprotective effects by influencing autophagy and inflammatory gene expression. Algal-derived vitamins (C and E) and minerals (magnesium, selenium, and zinc) contribute to immune regulation and pain modulation. Additionally, sulfated polysaccharides suppress microglial activation in the central nervous system (CNS). Marine algae represent a promising natural source of bioactive compounds with potential applications in pain management. Although current evidence, primarily derived from preclinical studies, indicates beneficial effects in various pain models, further research is necessary to confirm their efficacy, safety, and mechanisms in human populations. These findings advocate for the continued exploration of marine algae as complementary agents in future therapeutic strategies. Full article

The development of orally bioavailable non-peptidomimetic glucagon-like peptide-1 receptor agonists (GLP-1RAs) offers a promising therapeutic avenue for the treatment of type 2 diabetes mellitus (T2DM) and obesity. An extensive in silico approach combining structure-based drug design and ligand-based strategies together with pharmacokinetic properties and drug-likeness predictions is implemented to identify novel non-peptidic GLP-1RAs from the COCONUT and Marine Natural Products (CMNPD) libraries. More than 700,000 compounds were screened by shape-based similarity filtering in combination with precision docking against the orthosteric site of the GLP-1 receptor (PDB ID: 6X1A). The docked candidates were further assessed with the molecular mechanics MM-GBSA tool to check the binding affinities; the final list of candidates was validated by running a 500 ns long MD simulation. Twenty final hits were identified, ten from each database. The hits contained compounds with reported antidiabetic effects but with no evidence of GLP-1 agonist activity, including hits 1, 6, 7, and 10. These findings proposed a novel mechanism for these hits through GLP-1 activity and positioned the other hits as potential promising scaffolds. Among the studied compounds—especially hits 1, 5, and 9—possessed strong and stable interactions with critical amino acid residues such as TRP-203, PHE-381, and GLN-221 at the active site of the 6X1A-substrate along with favorable pharmacokinetic profiles. Moreover, the RMSF and RMSD plots further suggested the possibility of stable interactions. Specifically, hit 9 possessed the best docking score with a ΔG_bind value of −102.78 kcal/mol, surpassing even the control compound in binding affinity. The ADMET profiling also showed desirable drug-likeness and pharmacokinetic characteristics for hit 9. The pipeline of computational integration underscores the potential of non-peptidic alternatives in natural product libraries to pursue GLP-1-mediated metabolic therapy into advanced preclinical validation. Full article