Five previously undescribed compounds including three γ-aminobutyric acid (GABA)-containing cyclic peptides, unguisins L-N (1-3), and two diphenyl ethers, aspergillusethers K and L (4 and 5), were isolated from the fungus Aspergillus unguis SCSIO 41322 along with nine known compounds. The planar structures of these undescribed compounds were elucidated based on the combination of HRESIMS and 1D/2D NMR spectroscopic analyses. Furthermore, the absolute configurations of the undescribed cyclic peptides were elucidated by Marfey's method. In terms of bioactivity, compounds 1, 2, and 6 were identified as exhibiting anti-inflammatory activity for the treatment of inflammatory bowel disease (IBD) using a zebrafish wound injury inflammation model, in which 2 showing the greatest efficacy. Further studies demonstrated that 2 might alleviate inflammatory responses in vivo by inhibiting neutrophil recruitment, and effectively inhibits the progression of inflammatory bowel inflammation, exhibiting potential for the treatment of IBD.

Three new, previously undescribed tanzawaic acids, steckwaic acids H-J (1-3), and twenty-three known natural products (4-26) were isolated from the marine algicolous fungus Penicillium steckii SCSIO 41040. Structurally, compound 3 underwent a rare hydration reaction at the double bond of its carboxylic acid side chain. The chemical structures and stereochemistry were determined using comprehensive spectroscopic analyses, including NMR, electronic circular dichroism (ECD) calculations, and high-resolution electrospray ionization mass spectrometry (HRESIMS), and verified by literature comparison. The protective effect of tanzawaic acids on inflammatory damage to the intestinal epithelial barrier was assessed using an LPS-stimulated Caco-2/THP-1 co-culture model. Notably, immunofluorescence and Western blotting assays showed that compound 10 significantly enhanced the fluorescence signals and protein expression of ZO-1 and occludin, alleviated lipopolysaccharide (LPS)-induced intestinal barrier damage in Caco-2 cells, and contributed to the re-establishment of intestinal barrier homeostasis. Our findings demonstrate the critical role of tanzawaic acids in maintaining intestinal barrier integrity, identifying them as promising lead compounds for UC treatment.

Nine new mycophenolic acid derivatives, penicacids O-W (1-9), two first-time reported natural products (10, 11), and five known compounds (12-16), were isolated from a marine-derived fungus Penicillium senticosum RCDB005 found in a South China Sea sediment sample. Their structures were determined using NMR, HRESIMS, and optical rotatory dispersion (ORD) spectra, electronic circular dichroism (ECD) calculations, X-ray crystallography, and modified Mosher's methods. Eight of these compounds were evaluated for anti-proliferative effects against nine human cancer cell lines and the IC50 values ranged from nM to μM levels. Compounds 5, 7-9 showed potent inhibition activity against MOLM-13 acute myeloid leukemia cells with IC50 values between 0.13 and 1.13 μM.

Verlamelin A is a macrocyclic antifungal depsipeptide. In this study, a series of derivatives (1a-15a, 17a, 1b- 17b) were developed by replacing the l-Gln residue in verlamelin A with other proteinogenic l-amino acids. Biological evaluation revealed that compound 8b, substituted with an l-Thr residue, exhibited enhanced antifungal activity and an expanded spectrum against four plant pathogens─Alternaria alternata, Alternaria solani, Alternaria tenuissima, and Alternaria longipes─with minimum inhibitory concentration (MIC) values ranging from 4 to 32 μg/mL. Compound 12b, substituted with an l-Glu residue, showed antifungal activity against A. alternata, A. solani, and A. longipes, with MIC values ranging from 2 to 64 μg/mL. Both compounds demonstrated dose-dependent inhibitory effects on the mycelial growth of A. tenuissima and A. alternata, respectively. Structure-activity relationship studies indicated that compounds with the R configuration at the C-5 position of the tetradecanoic acid moiety exhibited broader spectrum of activity and greater potency than their S-configured counterparts. In vivo fruit infection assays showed that compounds 8b and 12b possessed curative efficacy, protecting tomatoes and apples from damage caused by these pathogens. With low toxicity, compounds 8b and 12b represent promising lead compounds for further development as antifungal agents to combat pathogens in agriculture.

Four new citrinin derivatives, monankarin G (1), monankarin H (2), penicilliode D (3), and (2S,3S)-2,3,4,6-tetramethyl-2,3-dihydrobenzofuran-5,7-diolone (4), along with nine known compounds (5-13), were obtained from the Mariana Trench-derived fungus Penicillium sp. SCSIO 41326. The accurate structures of new compounds, including absolute configurations were elucidated on the basis of NMR, MS, ECD and Mosher's ester method. All the compounds were evaluated for their enzyme inhibitory activity, the results showed that compounds 2, 4 and 6 exhibited weak acetylcholine esterase (AChE) inhibitory activity and compound 5 exhibited moderate neuraminidase (NA) inhibitory activity with an IC50 value of 87.0 μM.

Two unusual 13-membered macrocyclolipopeptides, cladosporiums A (1) and B (2), and four new steroids, cladosporisteroids D-G (3-6), were isolated from the Mariana Trench-derived fungus Cladosporium sp. RCDB004. Cladosporiums A (1) and B (2) possess an unprecedented macrocyclic skeleton formed by the condensation reaction of fatty acids and an alanine. The planar structures of isolated compounds were established by NMR and HRESIMS, with the stereochemical configurations further corroborated through X-ray crystallography. Notably, cocrystals of 1 were successfully obtained through the crystalline mate method.

Hepatitis B virus (HBV) infection continues to pose a significant threat to global public health. Current therapies, including nucleoside analogs and interferon-α, suppress viral replication but fail to eliminate covalently closed circular DNA (cccDNA) - a viral minichromosome essential for HBV persistence. Targeting cccDNA is critical for achieving a functional cure, yet few effective inhibitors have been reported. Building on our previously established HepG2-HBV/loxP cell model, we applied a high-throughput screening workflow to identify cccDNA-targeting agents from marine natural compounds. Screening a marine-derived natural product library identified five compounds that reduced hepatitis B surface antigen (HBsAg) secretion without notable cytotoxicity. Further validation in HepDES19 cells via hepatitis B e antigen (HBeAg) assays further narrowed candidates to two leads: W-609 (austinol) and KK8 (asperfatsine C), with IC50 values of 2.29 ± 0.41 and 2.97 ± 1.96 nM, respectively (compared to RG7834's IC50 of 2.00 ± 0.16 nM). Dose-response studies confirmed their anti-cccDNA activity: austinol exhibited IC50 values of 69.24 nM in HepG2-HBV/loxP cells and 2.23 μM in HepDES19 cells, whereas asperfatsine C showed IC50 values of 503.10 nM in HepG2-HBV/loxP cells but 10.66 μM in HepDES19 cells. Both compounds are derived from marine sources, exhibiting distinct structural features: austinol is characterized by a meroterpenoid scaffold incorporating a pentacyclic nucleus with a 6/6/6/6/5 ring system, while asperfatsine C contains an isoechinulin-type diketopiperazine skeleton with a long-chain fatty acid moiety. This study systematically screened a collection of marine-derived compounds using a recombinant cccDNA-based cellular model, leading to the identification of several promising anti-HBV inhibitors that facilitate drug development for chronic hepatitis B.

Five undescribed compounds (1-5), together with four known compounds (6-9) were isolated from the Antarctic-derived fungus Aspergillus ochraceopetaliformis SCSIO 05702. Their structures were elucidated by the nuclear magnetic resonance spectrum (NMR), mass spectrometry (MS). In addition, the absolute configurations of these compounds were determined by the combination of ECD and DP4+ calculations, chiral-phase HPLC analysis, Mosher's ester analysis and Mo2(OAc)4 induced circular dichroism method. Among them, 5 and 6 exhibited potent anti-inflammatory responses induced by LPS in RAW264.7 cells. Specifically, 5 and 6 were able to markedly inhibit the production of NO and pro-inflammatory cytokines including IL-6, TNF-α, and MCP-1 in RAW264.7 cells exposed to 0.1 μg/mL LPS. Moreover, they effectively upregulated the anti-inflammatory cytokines, such as IL-4, IL-10, and Arg-1 gene expression levels impaired by LPS without obvious cytotoxicity.

Naphthopyrones (NPs) are a class of heterocyclic molecules formed by the fusion of naphthalene and pyran ring. They are widely distributed in microorganisms, plants, and marine organisms, which have become a research focus in medicinal and synthetic chemistry due to their unique rigid skeleton, diverse biological activities, and controllable axial chirality. In recent years, with the innovation of synthesis technology and the in-depth analysis of the mechanism of action, the research on NPs has expanded from natural products discovery to functional oriented molecular design and application exploration. This article systematically reviews the structural diversity, pharmacological activity, and synthesis strategies of naphthopyrones compound. This is the first comprehensive review on NPs, which summarizing 226 compounds during the period of 1937 to December 2025, covering 161 articles laying the foundation for the development and utilization of NPs in the future.

Two new anthraquinone derivatives, (±)-1′-O-methyl-6-chloroaverantin (1a and 1b) and 6-chloroaverythrin (2), and one new diphenyl ether 1-((E)-but-2-en-2-yl)-3,8-dihydroxy-6-((E)-4-hydroxybut-2-en-2-yl)-4,9-dimethyl-11H-dibenzo[b,e][1,4]dioxepin-11-one (3), along with six known compounds, were isolated from the fungus Aspergillus sp. SCSIO 41331 collected from the deep-sea sediment in the cold-seep area of the South China Sea. Elucidation of planar structures was achieved via 1D and 2D NMR and mass spectrometry, whereas stereochemistry was validated through optical rotation and NOE correlations, chiral phase HPLC analysis and NMR calculation. All compounds were assessed for antitumor activity, among which compound 4 displayed moderate antiproliferative activity against HT29 cells and suppressed colony expansion.

Two new steroid derivatives, 3-oxoergosta-4,6,8(14),22-tetraen-27-oic acid (1) and (14R,24R)-14-methyl-24,25-dihydroxycholesta-4,8-dien-3-one (2), together with one anthraquinone (3), one amino acid derivative (4), five cyclic dipeptides (5-9) and a quinazolinone alkaloid (10), were isolated from a deep-sea-derived Aspergillus versicolor SCSIO 41325. Notably, compound 2 features an unreported cholesta-4,8-dien-3-one steroid scaffold among natural products. The structures were determined by NMR and high-resolution electrospray ionization mass spectroscopy (HR-ESI-MS) spectroscopic methods, single-crystal x-ray diffraction measurements and comparison with literature data. All isolated compounds were subjected to a broad range of biological assays, including tests against pathogenic bacteria and fungi, as well as for inhibition of pancreatic lipase, acetylcholinesterase, neuraminidase, and antioxidant activity evaluations.

Prostate cancer (PCa) remains one of the most common malignant tumors among men worldwide, typically relying on the androgen receptor (AR) signaling pathway. Inducing ferroptosis, a novel form of iron-dependent cell death, represents a promising strategy; however, its regulation by AR signaling is complex. The molecular chaperone heat shock protein 70 (HSP70) is critical for AR stability and function, yet its role as a therapeutic target in this context is underexplored. The anti-proliferative effect of the compound nidurufin (Nid) was assessed across PCa cell lines using MTT, clonogenic, and 3D spheroid assays. Ferroptosis was evaluated by transmission electron microscopy, reactive oxygen species (ROS) detection, and lipid peroxidation analysis. Mechanistic insights were gained through Western blot, qPCR, immunofluorescence, ChIP-qPCR, molecular docking, and cellular thermal shift assay (CETSA). In vivo efficacy was validated in a zebrafish xenograft model. Nid exhibited potent, selective anti-proliferative activity against AR-positive PCa cells, particularly 22Rv1 (IC₅₀ = 10.30 μM), and induced ferroptosis characterized by mitochondrial shrinkage and ROS accumulation. Mechanistically, Nid did not bind to AR, but it directly bound to HSP70, disrupting its chaperone function and leading to AR protein destabilization and transcriptional downregulation. This consequently suppressed the expression of the AR-target gene membrane-associated O-acyltransferase domain protein 2 (MBOAT2), a key ferroptosis suppressor enzyme. ChIP-qPCR confirmed AR directly binds the MBOAT2 promoter, and Nid treatment reduced this enrichment. In vivo, Nid significantly inhibited tumor growth and metastasis in a zebrafish xenograft model. Our study identifies Nid as a novel HSP70-targeted compound that triggers ferroptosis by disrupting the HSP70-AR-MBOAT2 axis. This work not only reveals a previously unrecognized connection between protein chaperone function and ferroptotic susceptibility but also positions HSP70 as a compelling therapeutic target for overcoming AR-pathway dependency in PCa.

Two new natural 2-alkylquinolin-4(1H)-one derivatives, 2-(5-methylheptyl) quinolin-4(1H)-one (1) and 2-(5-methylnonane) quinolin-4(1H)-one (2), along with ten known compounds (3-12), were isolated from the strain of Bacillus rugosus SCSIO 41395, which was obtained from the sediments of the Philippine Basin. All the isolates were evaluated for bacteriostatic activities against Pseudomonas aeruginosa (PA). Compounds 4 and 5 exhibited bacteriostatic effects by inhibiting the expression of rhl, pqs, and las quorum-sensing genes, as well as suppressing related phenotypes, including rhamnolipid, pyocyanin production, and biofilm formation. Our findings suggest that compounds 4 and 5 are promising quorum-sensing inhibitors for potential alternative treatments of PA infections.

Magnetospirillum gryphiswaldense MSR-1 is a model magnetotactic bacterium whose magnetosome biomineralization is closely linked to intracellular redox regulation. Although the periplasmic nitrate reductase NapA plays an essential role in denitrification and redox control, its biochemical properties in MSR-1 have remained unexplored. In this study, we constructed a heterologous co-expression system for MSR-1 NapA together with its cognate chaperone NapD, successfully producing soluble and biologically active recombinant NapA. The purified enzyme exhibited a characteristic iron-sulfur absorption band near 400 nm, and metal content analysis confirmed the presence of both iron and molybdenum cofactors. Electron paramagnetic resonance spectroscopy further demonstrated the presence of a redox-active [4Fe-4S] cluster and a Mo(V) center, indicating correct cofactor assembly. Enzymatic assays showed that MSR-1 NapA follows typical Michaelis-Menten kinetics toward nitrate, with optimal activity near neutral pH and moderate temperatures. These results establish MSR-1 NapA as a functionally active and structurally stable molybdoenzyme. Collectively, this work provides the first comprehensive biochemical characterization of NapA from a magnetotactic bacterium and offers a solid molecular foundation for understanding how nitrogen metabolism is coupled to redox regulation and magnetosome biomineralization in M. gryphiswaldense MSR-1.

One new fatty acid derivative (3Z,5E)-8-(hydroxymethyl)-2-(3-methoxy-2-methyl-3-oxopropyl)-4,6,10,12-tetramethyltetradeca-2,4-dienoic acid (1) and fifteen known compounds 2-16 were isolated from the Aspergillus sp. SCSIO41324 derived fungus from the deep sea. Comprehensive NMR experiments and high-resolution electrospray ionisation mass spectrometry data were combined to elucidate the structure of this new metabolite. All obtained constituents were evaluated for their bioactivities. Compound 2 showed mild neuraminidase inhibition, with an IC50 value of 74.44 μM. Subsequent molecular docking was performed to explore its binding modes with the enzyme.

Three novel derivatives of nucleoside (1), diaryl ether (6) and benzoquinone (11), along with 13 known compounds (2-5, 7-10, 12-16), were obtained from the ethyl acetate extract of the fungus Aspergillus sp. RCDB-W7. Structural elucidation was made through nuclear magnetic resonance (NMR), optical rotatory dispersion (ORD) spectra, high-resolution electrospray ionization mass spectrometry (HRESIMS), and electronic circular dichroism (ECD) calculations. The antibacterial and antileukemic activities of 16 isolated compounds were evaluated. Compounds 9 (64 μg/mL) and 10 (32 μg/mL) showed weak antibacterial activity against Staphylococcus aureus Newman, while none exhibited activity against Escherichia coli AB1157 or Klebsiella pneumoniae 210715XJ024 [MIC (minimum inhibitory concentration) above 64 μg/mL]. In the MOLM-13 acute myeloid leukemia cell line, compounds 1, 6, 8, and 9 showed weak cytotoxicity (cell viability 69.86%, 67.83%, 59.21%, and 56.18% at 50 μM, respectively), whereas compounds 10 and 14 displayed moderate activity (cell viability 33.45% and 29.31% at 50 μM, respectively).

As an emerging fiber material with promising application potential, lignocellulosic nanofibrils (LCNFs) have been widely explored for sustainable packaging with ultraviolet (UV)-blocking capability. However, strong intermolecular hydrogen bonding and structural heterogeneity often lead to aggregation of LCNFs, limiting their dispersion. Inspired by the sugaring-out strategy, this study fabricated a monosaccharide-promoted LCNF (MPL) film by incorporating monosaccharide to facilitate LCNF defibrillation and uniform dispersion, yielding finer nanofibrils with an average diameter of 12 ± 4 nm. The resulting films exhibited superior packaging performance, including high tensile strength (174.5 ± 1.2 MPa), excellent ultraviolet B (UVB) and ultraviolet A (UVA) blocking efficiencies of 99.9 ± 0.5% and 97.1 ± 0.7%, and low water vapor permeability (5.75 ± 0.02 × 10-11 g/m·s·Pa). Preservation tests on food further confirmed the effectiveness of the film in maintaining food quality. This work presents a high-performance strategy for developing biomass-based packaging materials.

To explore bioactive specialized metabolites from marine-derived fungi, four previously undescribed 2-pyridone alkaloids, oxalicpyridones A-D (1-4), two unreported tetramic acids, tolypocladenols G and H (5 and 6), together with five known 2-pyridone derivatives (7-11), were isolated from the marine-derived fungus Penicillium oxalicum SCSIO 41320. Their structures, including absolute configurations, were elucidated by extensive nuclear magnetic resonance (NMR) spectroscopic analysis, X-ray single-crystal diffraction, and calculations of electronic circular dichroism (ECD), 13C NMR, and optical rotation (OR). Additionally, oxalicpyridones A-C (1-3) inhibited the viability of several small-cell lung cancer (SCLC) cell lines in a dose-dependent manner. Among them, oxalicpyridone A (1) not only inhibited proliferation, induced apoptosis, and suppressed metastasis of SCLC cells in vitro, but also significantly inhibited the growth of SCLC cell-derived xenograft tumors in zebrafish in vivo. Collectively, these findings enrich the chemical diversity of marine-derived 2-pyridone alkaloids and provide potential lead compounds for anticancer drug discovery.

Two new tetraene lactone derivatives (1 and 2), two new α-pyrone derivatives (3 and 4), three compounds reported as natural products for the first time [an α-pyrone derivative (5), an indole-diketopiperazine alkaloid (6), and a β-amino acid derivative (8)], and 11 known compounds (7, 9-18), were obtained from microorganisms isolated from hadal trench sediments in the Pacific Ocean. Their structures were determined using NMR, HRESIMS, optical rotatory dispersion (ORD) spectra, NMR calculations followed by DP4+ analysis, electronic circular dichroism (ECD) calculations, X-ray crystallography analysis, and advanced Marfey's and modified Mosher eater methods. Microbial broth dilution assay suggested that compounds 6-11 and 15 had weak antibacterial effects.