Journal of Natural Products 最新文献

Three uncommon rearranged pregnane steroids, namely, sclerogroids A-C (1-3), along with seven known related ones 4-10, have been isolated from the soft coral Scleronephthya gracillimum collected off Ximao Island. The photoreactions of four α,β-unsaturated ketosteroids (8, 11-13) have been successfully performed, leading to the generation of two novel carbon skeleton pregnane steroids with an unprecedented 5/3/6/6/5 pentacyclic ring scaffold, namely, sclerogranes A (8b) and B (11f), together with a series of rearranged steroids and oxidation products. The structures of the new compounds were elucidated by a combination of spectroscopic analyses, time dependent density functional theory (TDDFT)-electronic circular dichroism (ECD) calculations, and comparison of the NMR data with those of known analogues. Bioassays demonstrated that compounds 1-4 and 8a exhibit significant antibacterial activity against various strains of vancomycin-resistant enterococci, as well as other pathogenic bacteria in humans and fish with minimum inhibitory concentration (MIC) values ranging from 1.9 to 29.6 μg/mL. In addition, compound 11c showed antineoplastic activity against HT-29 with an IC₅₀ value of 27.24 ± 2.87 μM, while compounds 8d and 11f exhibited anti-inflammatory activity by inhibiting the release of NO in RAW264.7 cells with IC₅₀ values of 15.4 ± 0.53 and 7.56 ± 0.93 μM, respectively.

Ten new 3,5-dimethylorsellinic acid-derived meroterpenoids featuring 6/6/6/6 or 6/6/6/5 ring systems, designated terretonins P–Y (1–10), together with one known analogue, lichtheiterpene A (11), were isolated from the soil-derived fungus Aspergillus sp. (strain TJ403–126). Planar structures incorporating absolute configurations were elucidated via a combination of HRESIMS, NMR spectroscopy, single-crystal X-ray diffraction analyses (Cu Kα), and electronic circular dichroism data analyses. Compounds 1–4 and 6–9 were evaluated for the herbicidal and antibacterial activities. The results revealed that compound 9 exhibited herbicidal activity against Medicago sativa (alfalfa), whereas compound 4 showed only weak inhibition. Compounds 4 and 6 demonstrated weak antibacterial effects against Escherichia coli, with inhibition zone diameters of 24.3 ± 0.3 mm and 25.4 ± 0.1 mm, respectively.

Four unreported compounds, including two pairs of spiroketal racemates, (±)-versilulin A (1a and 1b) and (±)-versilulin B (2a and 2b), and two diphenyl ether derivatives, versilulins C and D (3 and 4), together with four known compounds (5–8), were isolated from the endophytic fungus Aspergillus versicolor 347. The assignment of their structures was accomplished by spectroscopic analysis, including HRESIMS, NMR, chiral analysis, ECD calculation, and X-ray diffraction. Among them, compounds 1 and 2 possess an unprecedented 6/5/6/6 tetracyclic polyketide with a unique 1,4-dioxospiro[4.5]decan-8-one core skeleton. Compound 3 was characterized by an unusual 6/6/6/6/6/6 hexacyclic ring system featuring a rare 9-oxospiro[5.5]undecan-3-one. Compound 4 contains a novel 6/8/6/6/6/6 hexacyclic fused ring system. Biological assays revealed that compounds 3 and 5 displayed modest antibacterial activity against Staphylococcus aureus with an equal MIC value of 32 μg/mL.

An isoduprezianane-type sesquiterpene (1), with an unprecedented skeleton, along with rare isocedrenes (2–5) and known sesquiterpenes (6–11) were identified from the aerial parts of Ainsliaea pertyoides Franch. The structures, including absolute configurations, were established with a combination of NMR spectroscopy, single crystal X-ray diffraction analyses, and modified Mosher’s method. The effect of these compounds on HIF-2α expression was evaluated using a laboratory-developed 786-O/HRE reporter cell line, which was designed for screening of bioactive compounds targeting HIF-2α signaling in ccRCC. As a result, compounds 8–11 suppressed HIF-2α expression without apparent cytotoxicity and further inhibited HIF-2α-regulated endothelial cell tube formation at 5 μM.

The design of neurological “magic shotguns” represents a modern approach toward the treatment of complex central nervous system disorders, and many natural products like cannabidiol possess distinct potential due to their unique polypharmacological profiles toward central nervous system targets. Herein, we describe the computational design, semisynthesis, and preliminary biological screening of aminergic cannabidiol derivatives as neurological magic shotguns. A small library of 22 aminergic cannabidiol derivatives were synthesized and evaluated through radioligand binding assays, revealing that these derivatives generally exhibit higher affinity toward serotonin, dopamine and sigma receptors than the parent compound. Notably, compounds 8d and 8e displayed significantly improved affinity toward sigma-1 receptors (K_i = 4.8 nM and 8.3 nM, respectively). We then established the functional behavior of compound 8e in mouse primary hippocampal neurons through whole-cell patch clamp assays: exposure to compound 8e potentiates N-methyl-d-aspartate receptors, an effect that may be reversed in the presence of a selective sigma-1 receptor antagonist. These results suggest that compound 8e behaves as an agonist of sigma-1 receptors, thereby promoting downstream potentiation of N-methyl-d-aspartate receptors. Altogether, these findings provide preliminary evidence that aminergic cannabinoids, and potentially other derivatives of promiscuous natural products, may hold utility as neurological magic shotguns.

Natural products remain a primary source of new chemical entities and a central medium of biological communication. Among them, sulfur-containing natural products from microbes stand out for their diverse motifs─such as thioether (S–Cα/β/γ), thiazole, and sulfonate groups─distributed across RiPPs, NRPs, PKs, lipids, terpenoids, and hybrids. These sulfur-containing metabolites functionally contribute to communal interactions─intra- and interspecies microbe–microbe and microbe–host interactions─through their antibacterial, antifungal, antiviral, anticancer, and immunomodulatory activities. Crucially, they may act as information-rich signals that tune quorum circuits, biofilms, membrane and ion homeostasis, and host pathways. This review provides a structure- and mechanism-guided overview of sulfur-containing natural products reported over the past decade (2014–2025), covering their microbial sources, chemical diversity, as well as mechanisms of action and emphasizing how sulfur functionality encodes interaction strategies from host microbiomes to environmental systems.

Genome mining of fungal plant pathogens has uncovered biosynthetic gene clusters encoded on lineage-specific accessory chromosomes, revealing untapped potential for novel natural product discovery by metabolomic assessment of fungal populations. In Fusarium poae, a species contributing to Fusarium head blight on cereals, whole-genome sequencing and comparative metabolomics identified an accessory chromosome-associated biosynthetic gene cluster responsible for the production of a novel family of secondary metabolites, the fusadapamides. These linear tripeptides contain l-2,3-diaminopropionic acid (l-Dap), a rare nonproteinogenic amino acid not previously reported in fungi. Biochemical and genetic analyses revealed that F. poae synthesizes l-Dap via an accessory chromosome-encoded two-gene module that uniquely utilizes l-alanine as a substrate, diverging from known bacterial and plant l-Dap biosynthesis pathways. While fusadapamide production appears limited within Fusarium, homologous l-Dap biosynthetic modules were identified across diverse ascomycetes, suggesting a broader role in fungal secondary metabolism. This study highlights the power of using untargeted metabolomics at population-scale to uncover accessory chromosome-linked biosynthetic innovations and expands our understanding of fungal natural product biosynthesis.

Two unusual terpenoids, salviarobones A and B (1 and 2), were isolated from Salvia roborowskii guided by feature-based molecular networking. Salviarobone A (1) was a novel C₂₃-terpenoid featuring a unique 6/6/6/5/6 fused pentacyclic ring skeleton. Salviarobone B (2) was a norditerpenoid with an unprecedented 6/6/5 fused tricyclic ring system. Their structures and absolute configurations were unambiguously established by HRESIMS, NMR spectroscopic data, DP4+ analyses, ECD calculations, and single-crystal X-ray diffraction. It is also worth noting that 1 exhibits neuroprotective effect based on H₂O₂-induced oxidative damage in PC12 cells.

Three previously undescribed indole alkaloids, candindoles A–C (1–3), along with five known analogues (4–8), were isolated from the marine-derived fungus Aspergillus candidus HNNU0546. Structurally, 1 and 2 represent the first terphenyl-indole piperazine alkaloid hybrids featuring unprecedented backbones. Their structures including absolute configurations were elucidated by extensive spectroscopic methods, DP4+ probability analysis, and electronic circular dichroism (ECD) calculations. A plausible biosynthetic pathway for 1 is proposed. Compound 1 exhibited moderate growth-inhibitory activity against the plant pathogenic fungus of Alternaria sp. with an EC₅₀ value of 19.21 ± 0.26 μM, while compounds 1 and 2 showed significant cytotoxicity toward human rhabdomyosarcoma cells A673 with IC₅₀ values of 7.72 and 8.89 μM, respectively, comparable to the positive control cisplatin.

Pyrone derivatives, characterized by a six-membered lactone, exhibit multifaceted anticancer activity by targeting PI3K/Akt/mTOR, MAPK/ERK, Wnt/β-catenin, and Hedgehog pathways. They suppress cancer proliferation of various cancer cells, while inducing apoptosis through mitochondrial dysfunction and caspase activation. These compounds arrest cell cycle, downregulate cancer stemness markers, and reverse multidrug resistance and enhance chemosensitivity. Preclinical studies highlight efficacy in xenograft models, particularly against KRAS-mutated and therapy-resistant cancers, with synergistic effects when combined with chemo-/radiotherapy. Pyrone derivatives also impair angiogenesis by suppressing VEGF signaling. However, poor solubility and bioavailability, coupled with off-target toxicity hinder clinical translation. Emerging strategies, such as nanoparticle delivery, structural modifications, and immunotherapy combinations, aim to address these limitations. Their ability to disrupt oncogenic signaling, overcome resistance, and target cancer stem cells underscores their therapeutic potential. Future research should focus on pharmacokinetic refinement, toxicity profiling, and clinical validation to advance their application in precision oncology.