Journal of Natural Products 最新文献

Twenty-two new monoterpene-coumarins, comprising the initial disclosure of 11 enantiomeric pairings, were isolated from the rhizomes of Luvunga scandens with the aid of LC–MS/MS based on molecular networking. Luvunscandins A–G (1–7) are dihydrofurancoumarins with a furan ring connection, and luvunscandins H–K (8–11) are dihydrofurancoumarins connected through a pyran ring. Chemical structures and absolute configurations were determined by analysis of spectroscopic data and X-ray diffraction analysis. The neuroprotective effects of all the isolates on LPS-stimulated NO production in BV2 microglia were evaluated. Compounds 6a, 7a, 7b, 8b, 9a, 9b, 11a, and 11b demonstrated more potent inhibitory effects than the positive control PDTC. Structural–activity relationship analysis revealed that neuroprotective activity was primarily associated with pyran-type dihydrofurancoumarins or compounds bearing a C3′R,6′R configuration, whereas furan-type analogs or compounds with a C3′S,6′S configuration exhibited weak or no activity. (+)-Luvunscandin I (9a) showed the most significant inhibitory activity (IC₅₀ = 4.9 ± 0.6 μg/mL) through suppression of the inflammatory transcription factors p65NF-κB and iNOS.

Cyclotides are plant-derived macrocyclic peptides stabilized by a cystine-knot motif, found in a limited number of angiosperm plants. This study reports the discovery of the cyclotide, Spat1, from Spigelia anthelmia (Loganiaceae), expanding the phylogenetic range of known cyclotide-producing plants. Spat1, a 30-residue bracelet-type cyclotide, was isolated, purified, and sequenced de novo. It demonstrated strong bactericidal activity against the Gram-positive Bacillus subtilis (LC_99.9 = 20 μM) via rapid membrane disruption but showed no activity against Staphylococcus aureus or Gram-negative Escherichia coli (LC_99.9 > 400 μM). The selective lack of activity against S. aureus is unusual for antimicrobial peptides. The data suggest that Spat1’s activity is independent of lipoteichoic acid (LTA) in B. subtilis, suggesting that its mechanism involves interactions with cytoplasmic membrane phospholipids. The lack of phosphatidylethanolamine (PE) in S. aureus membranes and Spat1’s weak binding to LTA, combined with its low net positive charge (+1), likely explains its inefficacy against this bacterial species. Structural modeling using AlphaFold AfCycDesign indicated that Spat1 adopts a cyclotide-typical β-sheet architecture and a 3₁₀-helix within its loop regions. Overall, Spat1 broadens understanding of cyclotide diversity and evolution, highlighting their functional specialization and the convergent evolutionary pressures that shape their distribution across plant lineages.

Colobognatha, a group of millipedes (Diplopoda) known for their unique biological traits (e.g., brood care and sociality), is the only group among millipedes to produce terpenoid alkaloids. Before 2020, only four terpenoid alkaloids had been identified; however, recent studies have resulted in a surge of new chemical discoveries and research into their ecological and biochemical roles. In this review, we outline the social characteristics of Colobognatha, the chemical investigations of their defensive secretions, and the bioactivity of the terpenoid alkaloids with a particular emphasis on new findings. We conclude by summarizing gaps in the research on these chemicals and provide insights into future research directions.

Nine novel dihydro-α-pyrone derivatives, talaromypyrones A–I (1–9), were isolated from the soil-derived fungus Talaromyces sp. G23. These compounds share a conserved 3′R-configuration within the 4-hydroxy-5,6-dihydro-2-pyrone core but display notable variations in their flanking polyketide chains. Talaromypyrones A–H (1–8) demonstrate potent antibacterial activity against Gram-positive bacteria, including drug-resistant strains, while exhibiting excellent safety profile by showing no cytotoxicity toward normal human LO2 cells. However, they exhibit no activity against Gram-negative bacteria (likely due to their inability to penetrate the outer membrane) and fungi. Such antimicrobial profile, combined with the structural similarity to the α-pyrone antibiotic myxopyronin, suggests a potential target in the switch region of bacterial RNA polymerase (RNAP). Molecular docking studies revealed that talaromypyrone E (5) binds to the same site of RNAP as myxopyronin and forms additional hydrogen bonds between the 4-hydroxy-5,6-dihydro-2-pyrone core and the RNAP residues. Furthermore, talaromypyrones A (1) and D (4) demonstrate moderate anti-inflammatory activity, positioning 4-hydroxy-5,6-dihydro-2-pyrone core as a promising building block for the development of dual-function agents capable of concurrently addressing both conventional and drug-resistant bacterial infections while alleviating associated inflammatory responses.

Aster tataricus is a plant used in Traditional Chinese Medicine for the treatment of cough, phlegm, and asthma. Phytochemical studies of A. tataricus have resulted in the isolation of 23 peptides, among which the astins are recognized for their potential application as anticancer drugs. However, it was found that some of the astins, namely, astins C, F and G, are in fact produced by an endophytic fungus, Cyanodermella asteris, isolated from the inflorescences of the plant, while the remainder were suggested to be transformation products of these astins by A. tataricus. Using mass spectrometry imaging and microscopy, we demonstrate that astins exhibit a nonhomogeneous distribution, vary in relative abundance in different plant tissue sections, and are likely colocalized with fungal cells. To gain further insights into the diversity and composition of astins produced by C. asteris, we applied HPLC–MS/MS and mass spectrometry-based molecular networking after in vitro cultivation of the fungus in media with increased salinity. We found that the fungus produced a higher variety of astins than previously known, including several yet undescribed astins, suggesting that the fungus alone is indeed able to produce the complete astin diversity and that cross-species biosynthesis is unlikely.

A reexamination of the reported structure of isomallotusinin, previously proposed as an anomer of the ellagitannin mallotusinin, demonstrates that isomallotusinin is identical to mallotusinin, thus correcting a structural misassignment. This conclusion is supported by a detailed conformational analysis of mallotusinin, which bears a distinctive tetrahydroxydibenzofuranoyl (THDBF) group. Through a DFT-assisted analysis of ¹H–¹H coupling constants, we demonstrate that mallotusinin exists as a solvent-dependent equilibrium of ³S₁ and ¹C₄ conformers. Our findings resolve a structural ambiguity in the literature and highlight the importance of considering conformational dynamics in the structural elucidation of conformationally flexible ellagitannins.

Ipomoea funis Cham. & Schltdl. is an endemic vine found in central Mexico. The use of heart-cutting and peak-shaving methods in recycling preparative HPLC yielded funisin I (1), an undescribed resin glycoside, along with the known intrapilosins I (2) and V (3). Funisin I features operculinic acid A (6) as the oligosaccharide core. The structural similarities observed for funisin I align with those previously reported for purginoside I (4); however, a difference was apparent in the occurrence of dodecanoic and (−)-(2R)-methylbutyric acids as the long- and short-chain fatty acid substituents in compound 1. Moreover, the structure of the previously described acutacoside F (5) was corrected by comparing its NMR data with those of 1 and 4. The three isolated glycolipids (1-3) did not show intrinsic cytotoxicity. However, intrapilosin I (2), when combined (50 μM) with a sublethal concentration of the antineoplastic drug vinblastine at 0.004 μM, significantly improved its cytotoxic effect and ability to reverse the vinblastine-resistant phenotype in MCF-7 cells by arresting the cell cycle at the G2/M phase and acting as a competitive substrate for P-gp. Resin glycosides could become promising alternatives for developing new therapeutic combinatory strategies to combat multidrug resistance in cancer treatment.

Selective oxidation of tertiary carbons in steroids remains challenging due to their steric congestion and electronic similarity. Here, we identify the heterodimeric Fe(II)/α-ketoglutarate-dependent oxygenase TlxI–J as a highly versatile oxidative biocatalyst capable of targeting multiple sterically hindered positions across diverse scaffolds. TlxI–J accepts several steroid hormones and catalyzes distinct oxidations, including C-8β, C-9α, and C-14α hydroxylations and C-9/C-10 epoxidation. The enzyme also catalyzes the C-2/C-3 desaturation of flavanones, indicating broad substrate promiscuity beyond steroid frameworks. Docking studies suggest that the flexible lid-like loop and hydrophobic residues cooperate to position distinct scaffolds for selective oxidation. These results provide a foundation for engineering oxidative biocatalysts for the late-stage diversification of steroids and other complex molecules, and highlight the potential of TlxI–J for the chemoenzymatic synthesis of high-value steroid derivatives and related bioactive compounds.

This study established LC-MS-based metabolomics integrated with multivariate statistical analysis (UMMMS) to identify differential metabolites in Actinoalloteichus cyanogriseus under solid versus liquid culture conditions. Using this approach, 48 molecules exhibiting significant abundance differences between solid and liquid media were rapidly screened out. Among these, 8 were preliminarily identified as peptides potentially containing the unique β-Me-Leu residue by targeted MS/MS analysis. Guided by these screening results, 5 previously undiscovered peptides, designated as cyanogristatins A–E (1–5), were isolated. Their structures were elucidated using 1D/2D NMR spectroscopy, HR-MS/MS, and the advanced Marfey’s method. Furthermore, 5 effectively reduced the number of migrating inflammatory cell aggregates in a zebrafish model of inflammatory bowel disease at a concentration of 20 μM. In subsequent experiments using an in vitro organoid model, 5 did not exert direct epithelial protective effects; however, ELISA further revealed that it decreased the level of production of TNF-α in intestinal macrophages. This finding suggests that the anti-inflammatory effect of 5 is most likely mediated by the regulation of the cytokine TNF-α. In summary, this study demonstrates the potential of mass spectrometry technology for the comprehensive analysis of natural products, facilitating the rapid discovery of novel compounds and enhancing the exploration of microbial secondary metabolites.

Macro- and microalgae are primary producers in coastal ecosystems, and the former harbor diverse microbes. During our investigation of the fungi associated with estuarine macroalgae, Trichoderma spp. appeared predominant as epiphytes and exhibited no host affiliation. Furthermore, a dual culture of algicolous T. virens and T. longibrachiatum led to the production of 21 metabolites, including eight new terpenoids (1–3, 5–7, 11, and 12) and three new alkaloids (14, 15, and 21), identified by combined spectroscopic data. The terpenoids comprise four frameworks, especially the unusual eudesmane (3 and 4) in Trichoderma and the rare 6/7 fused ring system (11–13) in nature. Compounds 1, 3, and 4 feature characteristic halogenations, while 14 and 15 represent the first two hydroxylated derivatives at C-3 of gliotoxin. HPLC analysis revealed that 1, 3, 9–12, 14–16, and 21 were induced by the coculture. Among them, iodine-bearing terpenoid 3 was evaluated as the most broad-spectrum algicide against representative microalgae, which could cause harmful algal blooms. However, it only weakly inhibited the microalgae that can be used as bait in aquaculture and the zooplankton tested. This metabolite may be developed as a promising modulator of coastal microalgal communities.