A new nonribosomal peptide-polyketide (NRP-PK) hybrid, curvularisin (1), and a new polyketide, spiciferone D (2), together with twelve known compounds (3 - 14), were isolated from the mangrove-derived endophytic fungus Curvularia sp. P3. Their structures were established through extensive NMR and HRMS analyses, and the absolute configuration of 2 was confirmed by ECD comparison. Cytotoxicity evaluation on five cancer cell lines (4T1, HeLa, A549, Caco-2, and LLC) revealed a promising activity of compound 13 against LLC (IC50 = 5.9 μM), and a moderate effect of compound 12 against Caco-2 (IC50 = 49.2 μM). Additionally, compound 13 inhibited the growth of several bacterial strains, with MIC values ranging from 32 to 64 μg/ml.

Two new monoterpene-shikimate-conjugated meroterpenes, named phyllostictones J (1) and K (2), were isolated from the mangrove endophytic fungus Phyllosticta sp. E2A1, together with a new sesquiterpene-shikimate-conjugated spirocyclic meroterpene, named capitalensis E (3). The structures of 1-3 were elucidated by nuclear magnetic resonance spectroscopy (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), single-crystal x-ray diffraction analysis, electronic circular dichroism (ECD) calculations, and modified Mosher's method. Compounds 1-3 were evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Among them, compound 2 exhibited inhibitory activity with an IC50 value of 10.8 µM.

Chemical investigation of the mangrove endophytic fungus Aspergillus sp. H6a led to the isolation of six new compounds, including four naphtho-γ-pyrone dimers, aurasperones I-L (1-4), a monomeric precursor, rubrofusarin C (5), and a coumarin, ascoumarin A (6), along with 12 known analogues (7-18). Their structures and absolute configurations were established by spectroscopic data, ECD analysis, and the modified Mosher's method. Compounds 1-17 were evaluated for their cytotoxicity against A549 cancer cells using the CCK-8 assay. Compound 10 showed the most potent activity, with an IC50 value of 11.27 µM, comparable to cisplatin (DDP) (14.35 µM). In DDP-resistant A549/DDP cells, compound 10 retained potent activity with an IC50 value of 12.58 µM, markedly lower than that of DDP (40.19 µM), and further enhanced the inhibitory effect of DDP when used in combination. These findings expand the chemical diversity of mangrove-derived Aspergillus species and offer a candidate for overcoming DDP resistance.

Abstract Thirty-four chimeric pyridone alkaloids, including twenty-eight new compounds named aspernigrins F1−F8, G1−G5, H1−H7, and I−P (1−28), were isolated from the mangrove endophytic fungus Aspergillus niger H6a, together with six known ones (29−34). The structures of these compounds were elucidated by HRESIMS, NMR spectroscopic data, single-crystal X-ray diffraction analyses, TDDFT-ECD calculations, and chemical methods, including Marfey’s derivatization. The structure of 26 contains two units of 2-aminododecanoic acid, whereas those of 27 and 28 not only contain two moieties of 2-aminododecanoic acid but also possess an ester-linked neo-inositol group, featuring unprecedented chimeric pyridone alkaloids with amphiphilic properties. Compound 26 exhibited antibacterial activity against Enterococcus faecalis and Micrococcus luteus with minimum inhibitory concentration values of 8.0 and 16.0 μg/mL, respectively, whereas compound 27 displayed anti-tumor activity against the Hela cell line with an IC50 value of 15.9 μM. Further studies disclosed that 27 exerted concentration-dependent anti-tumor activity against HeLa cells, including the inhibition of cell proliferation, invasion, and migration, along with the successful induction of mitochondrial-mediated cell apoptosis and the arrest of cell cycle in the G0/G1 phase. This work provides insight into the discovery of new pyridone alkaloids as lead compounds for the development of anti-bacterial and anti-tumor agents.

Natural pigments and dyes provide a rich interface between biodiversity and chemistry, offering structurally diverse molecules with distinctive reactivity and bioorganic relevance. These compounds occur in plants, marine organisms, fungi, bacteria, insects, birds, animals, and mineral sources. They encompass major chemical classes such as carotenoids, tetrapyrroles and their degradation products. Owing to their biocompatibility and natural origin, these pigments are increasingly explored as safer alternatives to synthetic dyes and as functional ingredients in food, cosmetic, textile, and pharmaceutical applications. In recent years, these natural pigments have gained significant attention as bioactive molecules with antioxidant, anti-inflammatory, antimicrobial, antiviral, anticancer, neuroprotective, hepatoprotective, and immunomodulatory potential, exhibiting beneficial effects in preventing chronic disorders like diabetes, cardiovascular and degenerative eye diseases. This review provides an integrated examination of biodiversity, chemical classes, biosynthetic logic, structure-activity relationships, and biological properties of these natural pigments and dyes. Key challenges related to chemical stability, bioavailability, and scalable production are discussed, together with emerging biotechnological strategies designed to enhance their stability and sustainable supply.

In the search for novel natural products with hepatoprotective effects against acetaminophen-induced acute liver injury, the marine-derived fungus Aspergillus aculeatinus WHUF0198 was investigated. Seventeen undescribed pyranopyridone alkaloids, aculeapyridones A-Q (1-17), were isolated by bioactivity-guided fractionation of an extract obtained by coculture of the A. aculeatinus WHUF0198 with the mangrove-associated fungus Penicillium sp. DM27. Notably, compounds 12-15, which possessed a unique N-methoxy group, were identified as activation products of fungal coculture in liquid media. The structures and absolute configurations of these compounds were elucidated using a combination of universal spectroscopic techniques (NMR and HR-ESI-MS), ECD calculations, and single crystal X-ray diffraction analysis. All the isolated compounds, except 8 and 17, were evaluated for their hepatoprotective activity against acetaminophen-induced acute liver injury in vitro. Compounds 1-7, 9, 10 and 12-15 increased cell viability and reduced alanine aminotransferase (ALT) levels of acetaminophen-induced murine hepatocytes at either 5 or 10 mu M.

Three new phthalide derivatives, named dicymalides A-C (1-3), were isolated from the mangrove endophytic fungus Dicyma sp. L6B1, together with eight known compounds. The structures of these compounds were elucidated by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopic data, single-crystal X-ray diffraction analysis, and specific rotation quantum-chemical calculations. Inhibitory activities of 1-11 against nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells were evaluated. Compound 8 exhibited potent inhibitory activity with a half-maximal inhibitory concentration value of 1.0 µM.

A total of 12 new compounds, named fuscoposides A-L (1-12), including 2 phenolic, 9 benzenoid, and 1 phenylethanoid glucosides, were isolated from the mangrove endophytic fungus Fuscoporia sp. A2A6. The structures of these compounds were established by HRESIMS, NMR spectroscopic data, single-crystal x-ray diffraction analysis, and chemical methods. Most notably, 10 compounds, namely, fuscoposides A-I (1-9) and fuscoposide L (12), are mono- or di-chlorinated. Fuscoposide C (3) exhibited moderate neuroprotective effects against H2O2-induced oxidative damage in mouse hippocampal neuron HT-22 cells in a dose-dependent manner at the concentration range of 2.0-6.0 µM, whereas fuscoposide G (7) decreased the expression of COX2 in lipopolysaccharide-stimulated mouse microglia BV2 cells at the concentration of 5.0 µM, thereby displaying anti-inflammatory activity.

Discovery of new natural products with both anti-inflammatory effects on activated microglia and protective activity on dopaminergic neurons is a new strategy to find new drug leads against neuroinflammation in Parkinson's disease. In this work, nine new limonoids, named thaigranatumins A-I (1-9), and two new protolimonoids, named thaigranatumins J (10) and K (11), were obtained from seeds of the Thai mangrove, Xylocarpus granatum. The structures of these compounds were established by analysis of spectroscopic data, single-crystal X-ray diffraction (Cu Kα), and comparison of experimental and calculated ECD spectra. Thaigranatumin A (1), containing a C-16/C-30 δ-lactone ring-D and a tetra-substituted C8-O-C17-bridged tetrahydrofuran ring-F, is the first limonoid featuring a unique 6/6/6/6/6/5/5-fused heptacyclic framework. Thaigranatumin G (7) exhibited both inhibitory effects on the protein expression of iNOS, COX2, and IL-1β in lipopolysaccharide-stimulated mouse microglia BV2 cells and neuroprotective activity against rotenone-induced injury in mouse midbrain dopaminergic neuron MN9D cells in a dose-dependent manner. Preliminary bioassays indicated that thaigranatumin G might be a valuable lead against neuroinflammation, thus warranting further studies.

Phenylspirodrimanes are a class of structurally diverse meroterpenoids, including the bioactive dimer stachybocin A (1) and the high-reactivity monomer stachybotrydial (2), which are isolated from the genus Stachybotrys. Whereas the biosynthetic pathway of these phenylspirodrimane meroterpenoids has remained elusive. Herein, we deciphered the complete biosynthetic pathway of 2 with unprecedented two gene clusters and five discrete genes by genome mining, gene inactivation, heterologous expression, biochemical experiments, and especially combining with transcriptome-based hierarchical clustering and expression correlation analyses. Totally, 11 genes for the phenylspirodrimane core skeleton formation, 8'-methyl oxidation, and 3-OH epimerization were efficiently discovered and functionally characterized. Notably, these biosynthetic genes are distributed across seven distinct regions, with a rare combination of multiple gene clusters and genes outside the clusters. Bioactivity assays revealed that four intermediates 6-8, and 9a exhibited significant inhibitory effect on the inactivated state hNaV1.2 channels with IC50 values of 0.15, 0.04, 0.28, and 1.91 μmol/L, respectively. These findings expand our understanding of phenylspirodrimane-type meroterpenoid biosynthesis and underscore the utility of transcriptome-based hierarchical clustering and expression correlation analyses for identifying unclustered biosynthetic genes in fungi.

To date, metabolites of cryptomonads from the South China Sea have not been investigated. Herein, four new highly-oxidized steroids, named rhodomonasterols A-D (1-4), of which compounds 1, 2, and 4 possess a long-conjugated carbon chain, were obtained from the South China Sea cryptomonad Rhodomonas sp. The structures and absolute configurations of these steroids were unambiguously established by high-resolution electrospray ionization mass spectrometry, nuclear magnetic resonance spectroscopy, and single-crystal X-ray diffraction analyses (Cu-Kα). Notably, compounds 1 and 4 exhibited inhibitory activities against the production of nitric oxide (NO) in lipopolysaccharide-induced BV2 cells at the concentration of 10.0 µM. The two steroids inhibited the expression of inducible NO synthase, thereby displaying anti-inflammatory effects.

Skin protection and wound healing in harsh environments such as seawater, cold, and dryness face great challenges. However, traditional hydrogels tend to lose adhesion underwater, freeze at low temperatures, and dehydrate in dry environments, severely limiting their applications. Inspired by marine barnacles, a chitosan (CTS)-butyl acrylate (BA)-glycerol gel (CB-G-Gel) is fabricated, which mimic the electrostatic and hydrophobic interactions of barnacle cement proteins using CTS and BA respectively to enhance adhesion underwater, and employ a glycerol/water solvent exchange strategy to endow the gel with anti-freezing and water-retaining properties. CB-G-Gel exhibits strong underwater adhesion and good antibacterial activity, and promotes seawater-immersed wound healing. CB-G-Gel protects the skin from frostbite and scald (-196-120 degrees C), and has excellent water retention under dry conditions of 20 % relative humidity and 60 degrees C. This strategy of combining barnacle biomimicry with glycerol/water solvent exchange provides a guidance for skin protection and wound healing in harsh environments. (c) 2025 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Cancer incidence continues to increase every year. Scientists strive to search for new anticancer compounds to combat this disease. Appealingly, marine environmental niches are still an untapped scaffold for natural products with chemical and biomedical diversity. Hence, fungi isolated from the Red Sea sponge Spheciospongia vagabunda were explored. Two strains were purified from the sponge and identified, depending on 18 S rRNA gene sequence, as Aspergillus sp. (UR1) and Penicillium sp. (UR2). The obtained fungal extracts were submitted to LC-HR-ESI-MS metabolomics evaluation, which showed notable variation in the chemical profiles of both extracts. The cytotoxic activity was assessed against three cancer cell lines: HepG2 (hepatocellular carcinoma human), MCF7 (breast cancer) and CaCo-2 (human colon carcinoma), via MTT assay. UR1 extract displayed higher antiproliferative activity with IC 50 values 2.61 ± 0.12, 3.23 ± 0.21 and 3.41 ± 0.18 µg/ml against HepG2, CaCo-2 and MCF7, respectively. Whereas UR2 extract exhibited a less potent effect with IC 50 values of 17.65 ± 0.28, 18.38 ± 0.19, and 22.45 ± 0.27 µg/ml. Additionally, molecular docking was conducted. Most identified compounds established strong binding affinity with the PPARG gene. Compounds 6 and 16 showed binding energy with S values − 9.13 and − 8.38 kcal/mol, respectively. The findings suggested the importance of Spheciospongia vagabunda -derived fungi in the production of cytotoxic natural compounds that could be used for cancer management.

Two new paraherquamides (PHQs) namely aculeaquamides B and C (1 and 2), along with four known PHQs (3-6), were isolated from the co-culture of marine fungus Aspergillus aculeatinus WHUF0198 and mangrove-associated fungus Penicillium sp. DM27. Compound 1 represents the first PHQ derivative featuring an uncommon 7/6/5/5/6/5 hexacyclic system. The structures of the isolated compounds were elucidated based on exhaustive NMR spectroscopy measurement and HRESIMS data. The absolute configurations of new compounds were determined by TDDFT-ECD calculations. Compound 3 demonstrated suppression of AngII-induced cardiac hypertrophy while exhibiting relatively low cardiomyocyte toxicity.

Four new tremulane sesquiterpenes, named phaeosphaerienols A-D (1-4), and two new pyroglutamate-containing dipeptides, named phaeosphaeratides A-B (5-6), were isolated from the mangrove endophytic fungus Phaeosphaeriopsis sp. P11, together with a new 2-furancarboxylic acid derivative (7). Structurally, pheaosphaerienols A-C (1-3) are rare tremulanes containing a 1,10-epoxide moiety. The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and Marfey's derivatization method. All the isolates were evaluated for their cytotoxic, antibacterial, and DPPH free radical scavenging effects. However, none of the compounds exhibited obvious activities.

Hybrid fillers show great advantages in improving the frictional properties of epoxy (EP) composites. However, to date, achieving ultra-low coefficients of friction and wear rates in self-lubricating EP systems through the use of nanofillers remains a challenge. In this study, the hard diamond nanosheets, soft silver nanoparticles, dopamine hydrochloride, and 1H,1H,2H,2H perfluorodecyltrichlorosilane (FDTS) were designed to prepare organofluorinated Ag/2D diamond nanocomposites (NDs-fPDA-Ag NPs). The tribological tests demonstrated that 3 wt% addition of NDs-fPDA-Ag NPs in EP exhibited the best friction reduction and anti-wear properties, which were reduced by 84.3 % and 98.6% compared with pure EP. Significantly, it stands out as the sole instance reported to date that has successfully achieved the oil lubrication (average coefficient of friction 0.085 less than 0.1) in dry friction while maintaining ultra-low wear rate (4.9 x 10-6-6 mm3/(N & sdot;m)). 3 /(N & sdot;m)). The superior lubrication effect is primarily attributed to three key factors: the high hardness of the two-dimensional (2D) diamond nanosheets, which provides exceptional wear resistance; the "rolling effect" generated by the zero-dimensional (0D) silver nano- particles, which significantly reduces the friction coefficient; and the low surface energy of outermost grafted organofluorine compounds, which minimizes interactions between the NDs-fPDA-Ag NPs and the steel friction pair. The soft and hard combination of low surface energy 2D diamond greatly enhances the tribological performance of EP composites and provides a new approach for the preparation of excellent self-lubricating epoxy systems.

Fungi, a renewable natural product resource trove, have garnered increasing attention recently. Aspergillus niger (A. niger) Ma001, a subspecies isolated from the human gut, exhibited moderate in vitro inhibition of carbapenem-resistant Acinetobacter baumannii (CRAB). However, research on its active ingredients remains insufficient. Therefore, chemical investigations of A. niger Ma001 resulted in the isolation and identification of 19 natural products. Among these, two were identified as new compounds: a coumarin dimer with an unusual 3,8' carbon bridge, designated as 7,7'-di-O-demethyl-3,8'-bisiderin (1), and a 3-hydroxyanthranilic acid derivative (9). Their structures were elucidated through comprehensive analyses utilizing mass spectroscopy and nuclear magnetic resonance. Bio-evaluations indicated that some of these compounds exhibited antibacterial, anti-inflammatory, or anticancer activities.

Ten new limonoids, named xylomolones E-N (1-10), and two new protolimonoids, named xylomolones O (11) and P (12), were isolated from seeds of the Thai mangrove Xylocarpus moluccensis, together with the known compound, hispidone acetonide (13). The structures of these compounds were established by extensive NMR spectroscopic data, single-crystal X-ray diffraction analysis, and comparison of experimental ECD spectra. The absolute configurations of xylomolones E (1) and L (8) were unambiguously determined by single-crystal X-ray diffraction analyses, conducted with Cu Kα radiation. Xylomolones E-L (1-8) are mexicanolide-type limonoids, among which xylomolones J (6) and K (7) contain a C7/C28δ-lactone ring, whereas xylomolones M (9) and N (10) are phragmalin-type limonoids. Xylomolones O (11) and P (12) are two new protolimonoids. In addition, the 1H and 13C NMR spectroscopic data for hispidone acetonide (13) was first assigned completely. In bioassay, xylomolones F (2), M (9), and P (12) exhibited moderate inhibitory activity against the production of NO in LPS-induced RAW 264.7 cells with IC50 values of 31.54 ± 7.27, 62.84 ± 17.62, and 22.7 ± 6.56 μM, respectively.

Phenylspirodrimanes are a kind of meroterpenoids with structural diversity and complexity, exhibiting a wide of biological properties, especially for the lactam derivatives consisting a gamma-lactam moiety and N-linked side chains. These compounds were derived from multi-step combination of enzymatic and non-enzymatic conversions of intermediates in their biosynthetic pathways. Stachbotrydial (2) with an o-phthalaldehyde unit was supposed as the high-reactivity intermediate of phenylspirodrimane lactams via nonenzymatic reaction with amines. In the present work, an effective and non-enzymatic diversification strategy was developed for the structural diversification of phenylspirodrimane lactams including monomers and dimers from 2 by feeding structurally various mono- and diamines in the fungus Stachybotrys chartarum cultures. In total, 24 phenylspirodrimane lactams (1, 3-25) including 18 new compounds were synthesized. Among them, stachybocin A (1), a bioactive phenylspirodrimane lactam dimer, was produced with the yield of 18.7 mg/g of cell dry weight. The structures of these compounds were elucidated by extensive spectroscopic data, single-crystal X-ray diffraction (Cu K alpha), and calculated electronic circular dichroism (ECD) analyses. Bioassay revealed that compounds 1, 17, and 24 displayed significant inhibitory effect on the inactivated state of hNa(V) 1.2 channels with IC50 values of 0.22, 2.08, and 0.53 mu mol/L, respectively. In addition, 1 showed potent protein tyrosine phosphatase 1B (PTP1B) inhibitory, N-methyl-D-aspartate (NMDA) receptor antagonistic, and anti-inflammatory activities. (c) 2023 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

A new terrein dimer named lichtheicol A (1) and a new meroterpene named lichtheiterpene A (2), were isolated from the mangrove endophytic fungus Lichtheimia sp. J2B1, together with 10 known compounds (3-12). The planar structures and absolute configurations of 1 and 2 were established by a combination of extensive spectroscopic data analyses and electronic circular dichroism (ECD) calculations. Compounds 4 and 5 exhibited marked inhibitory effects against butyrylcholinesterase (BuChE) with IC50 values of 0.71 and 0.53 mu M, respectively.