Search Results (137)

Domoic acid (DA) is a neurotoxic terpenoid compound produced by certain marine algae. It accumulates through the food web and poses a significant threat to humans and animals by selectively targeting hippocampal neurons, leading to neuronal degeneration, necrosis, and subsequent memory impairment. The primary mechanism involves its potent agonism at glutamate receptors, which induces excessive calcium influx, resulting in excitotoxic cell swelling and death. Recent studies have further elucidated the critical role of downstream oxidative stress and other pathogenic factors in DA-induced neurotoxicity. These insights into its multifaceted mechanism have paved the way for novel therapeutic strategies, highlighting promising directions for future treatment development. Full article

Endoperoxides constitute a distinctive class of highly oxygenated terpenoids defined by the presence of a cyclic peroxide (–O–O–) bond, a structural motif responsible for their pronounced chemical reactivity and diverse biological effects. Naturally occurring endoperoxide-containing terpenoids are broadly distributed across terrestrial and marine taxa, including higher plants, algae, fungi, and bryophytes, where they are believed to participate in chemical defense and ecological interactions. This review provides a comprehensive overview of naturally occurring endoperoxide terpenoids, focusing on their natural sources, structural diversity, and reported biological activities. Particular emphasis is placed on compounds exhibiting antiprotozoal and antitumor activities, exemplified by artemisinin and its derivatives, which remain cornerstone agents in antimalarial therapy and continue to attract interest for their anticancer potential. Structure–activity relationship (SAR) analysis, supported by computational prediction using the PASS (Prediction of Activity Spectra for Substances) platform, is employed to examine correlations between peroxide-containing frameworks and biological function. Comparative assessment of experimental data and predicted activity profiles identifies key structural features associated with antiprotozoal, antineoplastic, and anti-inflammatory effects. Collectively, this review highlights endoperoxides as a valuable and chemically distinctive class of bioactive natural products and discusses their promise and limitations as leads for further pharmacological development, particularly in light of their intrinsic reactivity and stability challenges. Full article

Mangrove ecosystems along the Indian Ocean coast show great biodiversity, adapting to harsh environmental conditions of high salinity and higher organic matter, and they are a host for a range of microbial communities with special features that produce unique secondary metabolites. Of this, mangrove-associated endophytic fungi, the second largest ecological group of marine fungi, show the greater potential, being a diverse pool for discovering novel bio-actives with pharmacological and biotechnological interest. This review summarizes the research findings on structural diversity and the associated pharmacological activities of secondary metabolites produced by mangrove-associated fungi along the Indian Ocean coast reported over the period of 2002–2025, based on the literature retrieved from Google Scholar. The total of 302 secondary metabolites is presented mainly from classes of polyketides (208), alkaloids (34), and terpenoids (60). Interestingly, 164 compounds were identified, as first reported in those publications. These compounds have been reported to show diverse biological activities, and the most prominent activities are cytotoxic, antibacterial, antifungal, antioxidant, enzyme inhibitory, and anti-inflammatory effects. The structural novelty and pharmacological activities of these metabolites highlight the importance of mangrove fungi as promising sources for new drug discovery and advancing industrial biotechnology. Therefore, this review highlights the insight into the possible application of these chemical compounds in the future drug industry, as well as in biotechnology for advancing human well-being. Furthermore, though significant progress has been made in exploring the fungi community from mangroves of the African and Middle Eastern coasts, the Indian coast mangrove fungi are yet to be explored more for novel discoveries. Full article

Marine sponges possess complex metabolic systems that support their growth, physiology, and ecological interactions. However, the primary metabolic capacity of the sponge hosts remains incompletely characterized at the molecular level. In this study, we performed de novo transcriptome sequencing of a pooled sample of three individuals of Xestospongia sp. collected in Vietnam, using a high-throughput Illumina sequencing system, to characterize the host-derived metabolic pathways. A total of 43,278 unigenes were assembled, of which 69.15% were functionally annotated using multiple public databases. Functional annotation revealed a broad repertoire of genes associated with core metabolic pathways, including carbohydrate, lipid, and sterol metabolisms, as well as cofactor-related processes. Specifically, complete pathways involved in folate biosynthesis, terpenoid backbone biosynthesis, ubiquinone (Coenzyme Q) metabolism, and steroid biosynthesis were identified, reflecting the independent metabolic framework of the sponge host. Several highly expressed genes related to these pathways, including COQ7, ERG6, NUDX1, QDPR, and PCBD, were detected, and their expression patterns were confirmed by quantitative RT-PCR. Furthermore, protein-based phylogenetic analyses indicated that these genes are closely related to homologous proteins from other sponge species, supporting their host origin. This study provides the first comprehensive transcriptomic resource for Xestospongia sp. from Vietnam, and offers baseline molecular insights into the primary metabolic capacity of the sponge host. These data establish a foundation for future investigations of sponge physiology and host–microbe metabolic partitioning. Full article

Arboviruses such as dengue (DENV), Zika (ZIKV), and chikungunya (CHIKV) remain major global health threats, especially in tropical regions, with no effective antiviral treatments available. Recent research highlights progress in identifying antiviral compounds from natural sources against arboviruses belonging to the flavivirus genus, such as DENV and ZIKV. These compounds, derived from plants, marine organisms, and microorganisms, fall into several key chemical classes: quinones, flavonoids, phenolics, terpenoids, and alkaloids. Quinones inhibit viral entry and replication by targeting envelope proteins and proteases. Flavonoids disrupt RNA synthesis and show virucidal activity. Phenolic compounds reduce expression of non-structural proteins and inhibit enzyme function. Terpenoids demonstrate broad-spectrum activity against multiple arboviruses, while alkaloids interfere with early infection stages or viral enzymes. To support the reviewed literature, we performed molecular docking analyses of selected natural compounds and some arboviral proteins included as illustrative examples. These analyses support the structure–activity relationships reported for some natural compounds and highlight their potential interactions with essential viral targets such as the NS2B-NS3 protease and NS5 polymerase. Together, these literature and computational insights highlight the potential of natural products as scaffolds for antiviral drug development. Full article

Marine-derived species of the genus Alternaria are widely distributed across diverse aquatic habitats, functioning as pathogens, endophytes, and saprophytes. These fungi are notable for their ability to produce structurally diverse secondary metabolites with potent bioactivities. Between 2003 and 2023, a total of 67 marine-derived Alternaria species were reported and investigated, collectively yielding 319 compounds. Most of these fungal isolates were from Chinese marine territories (53 species; ~79%), followed by isolates from Korea, Japan, India, Egypt, Saudi Arabia, and oceanic regions such as the Atlantic and Pacific. The fungal isolates were mainly obtained from marine plants (26 isolates) and marine animals (23 isolates), with additional sources including sediments (13) and seawater (3). Among the metabolites investigated in different screens, approximately 56% demonstrated measurable bioactivities, with anti-inflammatory (51 active compounds), antimicrobial (41 compounds), cytotoxic (39 compounds), and phytotoxic (52 compounds) activities being the most frequently reported. Additionally, compounds with antiparasitic, antidiabetic and antioxidant effects are reported. The chemical diversity of Alernaria-derived compounds spans multiple structural groups, including nitrogenous compounds, steroids, terpenoids, pyranones, quinones, and phenolics. Notably, compounds such as alternariol, alternariol monomethyl ether, and alternariol-9-methyl ether exhibit broad pharmacological potential, including antibacterial, antifungal, antiviral, immunomodulatory, and anticancer effects. Several metabolites also modulate cytokine production (e.g., IL-10, TNF-α), underscoring their relevance as immunomodulatory agents. Taken together, marine-derived Alternaria compounds represent a prolific and underexplored source of structurally and biologically diverse secondary metabolites with potential applications in drug discovery, agriculture, and biotechnology. This review provides an updated and comprehensive overview of the chemical and biological diversity of Alternaria metabolites reported over the past two decades, emphasizing their biomedical relevance and potential to inspire further research into their ecological functions, biosynthetic mechanisms, and industrial applications. Full article

Marine Aspergillus fungi, adapted to extreme marine environments (e.g., sediments, corals, mangroves), are prolific producers of structurally diverse secondary metabolites with significant bioactivities. This review comprehensively analyzes 340 novel natural products reported from 81 marine-derived Aspergillus strains over the past three years, classifying them into six major categories: alkaloids (31.2%), polyketides (29.4%), terpenoids, lignans, cyclopeptides, and others. Bioactivity assessments reveal broad therapeutic potential, including antitumor, antimicrobial, anti-inflammatory, and antiviral effects. Notably, marine sediments constitute the primary source (25.9% of strains), followed by sponges and corals. The predominance of alkaloids and polyketides underscores their pharmacological relevance. These findings highlight marine Aspergillus as a critical resource for drug discovery, offering promising scaffolds for developing treatments against human diseases and agricultural pathogens. Full article

Aging results from the combined effects of oxidative stress, chronic low-grade inflammation, mitochondrial decline, and cellular senescence, which together drive age-related disorders. Natural products ranging from polyphenols and terpenoids to alkaloids, polysaccharides, peptides, and marine metabolites can influence central pathways such as Nrf2/ARE, NF-κB, MAPK, JAK/STAT, AMPK/PGC1-α, mTOR, and SIRT1/FOXO. By doing so, they strengthen antioxidant defenses, temper inflammation, preserve mitochondrial balance, and regulate autophagy. There is increasing attention to synergy, where combinations of bioactives can achieve stronger and more balanced effects than single agents alone. Advances in artificial intelligence are accelerating this discovery process, while greener extraction and smarter delivery systems such as deep eutectic solvents and nanostructured carriers are improving bioavailability and consistency. Together, these developments underscore the promise of natural product-based strategies for healthy aging. Grounded in rigor and reproducibility, this Special Issue aims to inspire translational advances toward healthier and more graceful aging. Full article

Mangroves represent a promising yet underexplored source of natural products. Sonneratia caseolaris (mangrove apple) is a widely distributed species with a long history of use in traditional medicine, and it is receiving increasing recognition for its bioactive secondary metabolites. Research has expanded in recent decades, but findings remain dispersed across diverse sources, complicating interpretation of its chemistry and pharmacological potential. This review consolidates four decades of investigations, documenting 141 identified compounds from studies largely restricted to India, Bangladesh, Indonesia, and China and focusing on leaves, fruits, bark, stems, and twigs, with roots notably unexplored. The phytochemical profile is dominated by phenolic acids, flavonoids, and tannins, alongside terpenoids, steroids, fatty acids, fatty alcohols, aldehydes, hydrocarbons, and polysaccharides. The most extensively studied activities are antioxidant and antimicrobial, with extracts consistently exhibiting strong free-radical scavenging capacity and broad-spectrum antibacterial and antifungal effects, including efficacy against drug-resistant strains. Additional reports describe central nervous system depressant, antidiarrheal, metabolic, anti-inflammatory, analgesic, antipyretic, and anti-allergic activities. In contrast, anticancer investigations remain scarce, despite promising outcomes reported for related mangrove taxa. By consolidating and critically evaluating the existing evidence, this review highlights the pharmacological potential of S. caseolaris and identifies key knowledge gaps to guide future marine drug discovery. Full article

Methicillin-resistant Staphylococcus aureus (MRSA), a multidrug-resistant pathogen, poses a significant threat to global healthcare. This review evaluates the potential of marine algal metabolites as novel antibacterial agents against MRSA. We explore the clinical importance of S. aureus, the emergence of MRSA as a “superbug”, and its resistance mechanisms, including target modification, drug inactivation, efflux pumps, biofilm formation, and quorum sensing. The limitations of conventional antibiotics (e.g., β-lactams, vancomycin, macrolides) are discussed, alongside the promise of algal-derived compounds such as fatty acids, pigments, polysaccharides, terpenoids, and phenolic compounds. These metabolites exhibit potent anti-MRSA activity by disrupting cell division (via FtsZ inhibition), destabilizing membranes, and inhibiting protein synthesis and metabolic pathways, effectively countering multiple resistance mechanisms. Leveraging advances in algal biotechnology, this review highlights the untapped potential of marine algae to drive innovative, sustainable therapeutic strategies against antibiotic resistance. Full article

Marine-derived fungi have proven to be a rich source of structurally diverse terpenoids with significant pharmacological potential. This systematic review of 119 studies (2020–2024) identifies 512 novel terpenoids, accounting for 87% of the total discoveries to 2020, from five major classes (monoterpenes, sesquiterpenes, diterpenes, sesterterpenes, and triterpenes) isolated from 104 fungal strains across 33 genera. Sesquiterpenoids and diterpenoids constitute the predominant chemical classes, with Trichoderma, Aspergillus, Eutypella, and Penicillium being the most productive genera. These fungi were primarily sourced from distinct marine niches, including deep sea sediments, algal associations, mangrove ecosystems, and invertebrate symbioses. Notably, 57% of the 266 tested compounds exhibited diverse biological activities, encompassing anti-inflammatory, antibacterial, antimicroalgal, antifungal, cytotoxic effects, etc. The chemical diversity and biological activities of these marine fungal terpenoids underscore their value as promising lead compounds for pharmaceutical development. Full article

Marine-derived Penicillium spp., including Penicillium citrinum, Penicillium chrysogenum, and Penicillium sclerotiorum, have emerged as prolific producers of structurally diverse secondary metabolites with cytotoxic activity. This review systematically categorizes 177 bioactive compounds isolated from marine Penicillium spp. between 2018 and 2024, derived from diverse marine environments such as sediments, animals, plants, and mangroves. These compounds, classified into polyketides, alkaloids, terpenoids, and steroids, exhibit a wide range of cytotoxic activities. Their potency is categorized as potent (<1 μM or <0.5 μg/mL), notable (1–10 μM or 0.5–5 μg/mL), moderate (10–30 μM or 5–15 μg/mL), mild (30–50 μM or 15–25 μg/mL), and negligible (>50 μM or >25 μg/mL). The current review highlights the promising role of marine Penicillium spp. as a rich repository for the discovery of anticancer agents and the advancement of marine-inspired drug development. Full article

This study aims to unveil the marine invertebrate Sidnyum elegans, a Mediterranean ascidian, as a natural resource for the early development of new treatments for triple-negative breast cancer (TNBC). Nine different fractions obtained via medium-pressure liquid chromatography (MPLC) of the butanol-soluble material of the ascidian were evaluated in proliferating MDA-MB-231 cells in a range of 10–50 µg/mL. Among them, the SEB-5 fraction was found to be the most effective in reducing cell proliferation and concomitantly inducing apoptosis, revealed via MTT assay and FACS analysis using Annexin V/PI dual staining. Furthermore, we investigated the effect of this fraction on cell cycle phases, revealing that SEB-5 can arrest the cells in the G0/G1 phase. This latter effect was then confirmed via transcriptomic analysis, showing that treatment with SEB-5 reduced the expression of cyclinB1, CDC25a, and CDK1. Finally, to evaluate the potential antimetastatic effect of SEB-5, a wound-healing assay was performed showing the ability of SEB-5 to reduce MDA-MB-231 cell migration. The chemical characterization of SEB-5 components was performed using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS/MS) and nuclear magnetic resonance (NMR) spectroscopy. This analysis revealed the presence of a terpenoid and polyketide-like compounds, including the alkyl sulfate 1 and phosphoeleganin 2, along with three novel phosphoeleganin-related products 3–5. Full article

Parasitic diseases pose a serious threat to the health of humans and the steady development of livestock husbandry. Although there are certain drug-based treatment methods, with the widespread application of drugs, various parasites are gradually developing drug resistance. Natural products are highly favored by researchers due to their characteristics such as low toxicity, multi-target effects, and low risk of drug resistance. The ocean, as the largest treasure trove of biological resources on Earth, has a special ecosystem (high pressure, high salt, and low oxygen). This enables marine organisms to develop a large number of unique structures during their survival competition. So far, a variety of compounds, such as terpenoids, have been isolated from the algae. As potential drugs, these compounds have certain curative effects on various diseases, including tumors, parasitic diseases, Alzheimer’s disease, and tuberculosis. This paper systematically reviews and analyzes the current advances in research on the antiparasite effects of seaweed extracts. The primary objective of this research is to formulate a conceptual foundation for marine pharmaceutical exploration, focusing on the creation of innovative marine-based medicinal compounds to overcome the emerging problem of parasite resistance to conventional treatments. Full article