Journal of Natural Products 最新文献

Cannabidiol(CBD) exhibits broad anti-inflammatory andneuroprotectiveeffects. Although CBD has been reported to act on multiple moleculartargets, the direct protein interactors and molecular mechanisms underlyingits complex pharmacological activities remain incompletely understood.In this study, we developed a biotinylated CBD probe (II-2) and aFITC-labeled CBD fluorescent probe (III-3) for affinity enrichmentand cellular imaging, respectively. Probe-mediated target fishingidentified UDP-glucose dehydrogenase (UGDH) as a potential CBD-interactingprotein. Competitive pull-down and western blot analysis showed thatthe CBD-derived probe specifically enriched UGDH, and this enrichmentwas competitively attenuated by excess CBD. Biolayer interferometrywas consistent with an apparent micromolar affinity association betweenCBD and UGDH under the assay conditions, with an apparent K_d of approximately 5.8 μM. Functionalassays showed that CBD enhanced UGDH enzymatic activity in a LPS-inducedinflammatory model without markedly altering UGDH protein expression.Immunofluorescence imaging further supported the intracellular spatialassociation between the CBD-derived fluorescent probe and UGDH. Thesefindings suggest that UGDH is a potential CBD-interacting proteinand provide an experimental basis for further elucidating the molecularbasis of CBD-related anti-inflammatory activity.

Streptomyces are vitalsources ofbioactive metabolites. From Streptomyces sp. AN091965 culture extracts, seven secondary metabolites wereidentified. Five showed nematicidal activity: spectinabilin (1), its unprecedented derivative (Z,E,E,Z)-spectinabilin (2), homoaureothin (3),undecylprodigiosin (4) and metacycloprodigiosin (5), while two spectinabilin derivatives, SNF 4435C (6) and SNF 4435D (7) were immunosuppressive.Subsequent biological assays demonstrated that compound 2 exhibited remarkable nematicidal activity, surpassing the commercialagent fosthiazate and showing comparable efficacy to abamectin. Thisstudy not only reports a novel nematicide but also demonstrates thestrain’s unique capacity to produce multiple nematicides, servingas a promising host strain for biopesticide production.

Theproposed structure of oleraciamide A was confirmedby the computationalmethods and synthesis. However, the structure of oleraciamide B wasfound to be incorrect and, therefore, reassigned as an amine N-oxide. The structure of the reassigned natural productwas confirmed through comparison with authentic material obtainedvia total synthesis.

β-Hydroxy-amino acids are key structural motifsof many bioactivenatural products, but enzymatic β-hydroxylation of an aromaticamino acid appears to be uncommon. In known cases, this reaction typicallyoccurs on a residue residing in a peptide scaffold or tethered ona carrier protein via a thioester linkage. EcdG, an α-ketoglutarate/Fe(II)-dependentdioxygenase involved in the biosynthesis of echinocandins, is an exception,catalyzing the stereoselective β-hydroxylation of a free l-homotyrosine amino acid. Here, we report a comprehensive structuraland mechanistic study of EcdG and use knowledge gained from this studyfor functional modulation of the homologous protein GloM. High-resolutioncrystal structures of EcdG in complex with α-ketoglutarate and l-homotyrosine were determined. With the association of site-directedmutagenesis, the molecular basis for substrate recognition and theregio- and stereoselectivity of EcdG was revealed and then used toguide the engineering of GloM. The substrate specificity and oxidationcapability of this homologous protein were altered, enabling selectivetransformation of the unnatural substrate l-homophenylalanineto either a β-hydroxyl product or a γ-keto product. Thiswork provides mechanistic insights into a type of uncommon β-hydroxylaseand expands the enzymatic toolbox for selective oxidative functionalizationof a free aromatic amino acid.

Boavistamide A (1),a new alkyne-containingcyclicdepsipeptide featuring the rare 3-amino-2-methyl-7-octynoic acid (AMOYA)moiety, was discovered along with two structurally related analogs,boavistamides B and C (2 and 3), from afilamentous marine cyanobacterium collected on Boa Vista Island, CaboVerde. Their isolation was guided by antiplasmodial activity, GNPSMS/MS molecular networking, LC-MS profiling, and dereplication usingthe MarinLit database. The planar structures of boavistamides A–C(1–3) were elucidated through comprehensiveHRMS and 1D/2D NMR analyses, with annotation support from AI-basedtools SMART-NMR 2.1 and DeepSAT. The absolute configurations wereestablished using Marfey’s analysis and l-Phe-OMecoupling, complemented by NMR-based conformational studies. BoavistamidesA and B exhibited moderate antiplasmodial activity with no mammaliancell cytotoxicity. Microscopic observations and metagenomic binningidentified the producer strain as belonging to the genus Okeania (Microcoleaceae). These results expand the chemical diversity ofAMOYA-containing cyanobacterial metabolites and highlight the utilityof integrated metabolomics and AI-assisted workflows for natural productdiscovery from environmental samples.

The genus Ocotea is a significant source of bioactive agents within the Lauraceae, yet it remains underexplored. Despite its ethnomedicinal relevance and chemical diversity, Ocotea species remain taxonomically challenging as they belong to the multifaceted “Ocotea complex”, a phylogenetically unresolved group. Moving beyond previous literature Ocotea surveys, this review provides the first curated, genus-specific data set of both volatile and nonvolatile specialized metabolites. Covering research articles from 1830 to 2025, this review provides the most comprehensive synthesis to date, documenting 984 unique chemical compounds across 115 species. This effort culminated in the construction of the Ocotea Chemical Database (OcoteaDB), a novel digital resource created to streamline the genus’s chemical diversity for the global scientific community. Furthermore, it presents current knowledge of biosynthetic routes leading to key bioactive scaffolds, including aporphinoid and benzylisoquinoline alkaloids, lignoids, glycosylated flavonoids, and a diverse array of terpenoids, while addressing the stereochemical and structural intricacies unique to the genus. This review lays a robust foundation to drive future Ocotea-focused bioprospecting studies and guides research in the fields of natural products, chemophenetics, metabolomics, and medicinal chemistry regarding the Ocotea species, its chemical scaffolds, and specialized metabolites.

A comprehensive chemical investigation of the extract from Phyllanthus hainanensis led to the isolation and identification of four new aromatic diterpenoids, phainanones A–D (1–4), along with one known analogue (5). Phainanones A (1) and B (2) are novel ent-cleistanthane-type diterpenoids, with 1 characterized as a 17-nor derivative and 2 as a 3-nor derivative, both sharing a rearranged 5/6/6 tricyclic ring system. Their structures with absolute configurations were established by comprehensive spectroscopic analysis, ECD calculations, and X-ray crystallography. Putative biosynthetic pathways for compounds 1 and 2 were also proposed. In biological assays, compounds 2–4 potently inhibited the HIV-1 Bal pseudovirus while showing low cytotoxicity (IC₅₀ 0.54–3.3 μM; CC₅₀ > 30). The most active compound 2 also exhibited strong activity against HIV-1_IIIB (IC₅₀ = 1.0 ± 0.11 μM, SI > 98). Furthermore, its time-dependent inhibition profile indicates that it may act at a postentry step, interfering with early viral replication events such as reverse transcription. This study highlights compound 2 as a promising lead for anti-HIV drug development.

Sarcobergilide A (1), featuring an uncommon 11/7/5 tricyclic ring system, a new flexibilane-based diterpenoid, sarcoberginol A (2), and seven new cembranoids 3–9 were isolated from the South China Sea soft coral Sarcophyton ehrenbergi. The structures of the new compounds were established by extensive spectroscopic analyses, X-ray diffraction, the quantum mechanical NMR (QM-NMR) method, and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1 was proposed. In the bioassays, a primary screen in LPS-stimulated RAW264.7 macrophages highlighted compound 3 as the most active compound, showing the greatest reduction of NO release and TNFα secretion among the isolates. In TNFα-stimulated MC38 cells, RNA-seq analysis showed that compound 3 downregulated inflammation- and immune-related transcriptional programs and dose-dependently mitigated TNFα-induced IκBα degradation, consistent with attenuation of TNFα-associated inflammatory signaling. Moreover, several compounds exhibited moderate inhibitory effects against six pathogenic bacterial strains, with MIC values ranging from 2 to 64 μg/mL.

Chemical investigation on fermented products by the fungal strain Westerdykella dispersa Ca4–13 isolated from edible oysters Crassostrea angulata collected from Taiwan resulted in the isolation of seven chemical entities. Their structures were elucidated by spectroscopic analysis to be westeroic acid A (1), westeroic acid B (2), westeroic acid C (3), auranticin A (4), auranticin B (5), pilobolusone C (6), and epi-radicinol (7). Among these, westeroic acid A (1) is a novel C₁₄ polyketide with a γ-lactone functionality, while westeroic acids B (2) and C (3) are two rare C₂₈ polyketides with a unique 6/6-spiro-linked δ-lactone moiety. Compounds 1, 2, 3, and 7 exhibited anti-inflammatory activities on nitric oxide production in lipopolysaccharide (LPS)-induced BV-2 microglial cells with IC₅₀ values ranging from 9.9 to 11.3 μM. Compounds 2 and 3 significantly suppressed LPS-induced inducible nitric oxide synthase (iNOS) protein expression. Molecular docking analysis using murine iNOS (PDB ID: 1QW4) provided structural insight into these observations, suggesting that effective inhibition was associated with cooperative interaction networks within the l-arginine binding pocket rather than a single dominant interaction. Overall, these findings highlight their promise as potential lead compounds for further neuroinflammation-related drug development.