Journal of Natural Products 最新文献

The Zika virus (ZIKV), an emerging orthoflavivirus, presents a significant public health threat due to its rapid dissemination and association with severe neurological complications. The urgent need for effective antiviral agents has driven research into novel bioactive compounds derived from unique natural sources. Microorganisms inhabiting extreme environments are particularly promising for such discoveries due to their potential to produce unique metabolites. In this study, we explored microorganisms from the underexplored French Polynesian microbial mats known as “Kopara” to identify new bioactive natural products. Using a molecular networking-based dereplication strategy, we investigated various culture and extraction techniques of the strain Nocardia otitidiscaviarum 20-S13, leading to the discovery of two novel glycoglycerolipids, otitiglycomycins A and B (1 and 2). Structure elucidation of these compounds was achieved through NMR spectroscopy, X-ray crystallography, and TDDFT-specific rotation prediction. We found that otitiglycomycin A (1), but not otitiglycomycin B (2), suppresses ZIKV infection at non cytotoxic concentrations without effects on cell viability. Time-of-drug addition assays along with virus inactivation and binding assays demonstrated that 1 neutralizes ZIKV infectivity by preventing the virus from attaching to the host cell membrane.

Cytochalasins are notable for their structural diversity and broad range of biological activities. The gene cluster responsible for the biosynthesis of cytochalasins bearing diverse polycycles was identified in Phomopsis sp. DHS-48. Characterization of the cluster indicated that only the 5/6/11-tricycle can be biosynthetically produced. The chemical space of cytochalasins was expanded by acid-mediated intramolecular cyclo-rearrangement of the 5/6/11-tricycle, and three new cytochalasins, phomoparagins D–F (13, 17, and 18, respectively), with diversified polycycles were obtained, among which compound 13 featured an unprecedented 5/6/5/7/6-pentacycle. Their structures and absolute configurations were established by spectroscopic analysis (1D, 2D NMR), electronic circular dichroism calculations, and a single-crystal X-ray diffraction experiment. The compounds inhibited the growth of HeLa and RKO cell lines with IC₅₀ values ranging from 0.8 to 47.3 μM. Cytoskeleton staining experiments and molecular docking models revealed that compound 13 showed cytotoxicity by targeting F-actin.

A novel family of antibiotics, MDN-0057 to MDN-0060 (1–4), was isolated from liquid cultures of the fungus Ophiosphaerella korrae. These compounds incorporate two isocyanide groups in their complex structures that were elucidated by extensive spectroscopic analyses, including HRESIMS, and 1D and 2D NMR experiments. The relative configurations were determined by using J-based configuration analyses and the interpretation of key NOESY correlations consistent with the existence of a major conformation in solution. Mosher ester derivatization analysis allowed the establishment of their absolute configurations. All four compounds displayed in vitro antibacterial activity with a broad spectrum against Gram-negative pathogens.

Malfilamentosides are a class of fungal secondary metabolites characterized by glycosylated furanone scaffold; however, the enzyme that catalyzes the O-glycosylation of the furanone core with N-acetylglucosamine (GlcNAc) has not yet been identified. In this study, we discovered and identified the biosynthetic gene cluster of the malfilamentosides. In vivo and in vitro investigations revealed that a glycosyltransferase, MftB, catalyzes the O-glycosylation of the furanone scaffold with GlcNAc. Furthermore, MftB exhibits broad promiscuity toward glycosyl donors and acceptors, highlighting its potential in glycoside production.

A bioassay-guided chemical investigation of the endophytic fungus Chaetomium nigricolor F5 resulted in the discovery of two novel sesquiterpenes, chamilactones A and B (1 and 2), with a new 9,10-seco-15-nor-isoilludalane carbon skeleton, together with several biosynthetically related precursors (3–8). Their structures and absolute configurations were elucidated by the analysis of MS, NMR, calculated ¹³C chemical shifts, ECD calculations, and single-crystal X-ray diffraction data. It was proposed that an unprecedented carbon–carbon bond cleavage between C-9 and C-10 in 3–8 was the key step in the biosynthetic pathway of 1 and 2. Compound 3 displayed potent neuroprotective effects by reducing the phosphorylation level of p65 and inhibiting its nuclear translocation in the TLR4-mediated NF-κB signaling pathway in LPS-induced BV2 microglial cells.

A marine-derived Pleosporales fungus, Uzbekistanica storfjordensis, was isolated from driftwood and described as a new species. The fungus was cultivated in liquid media and a molecular networking-driven approach was used to identify potential new secondary metabolites. The targeted compounds were isolated using preparative HPLC-MS, and through extensive spectroscopic analysis, eight new ophiobolin-type sesterterpenes, bipolarolides H–O (1–8), were identified. The absolute configurations of the compounds were determined by ECD assessment. Bipolarolide L (5), M (6), and O (8) exhibited inhibitory activity against Streptococcus agalactiae with MIC values of 86, 66, and 64 μM, respectively.

Bibenzyls and dihydrophenanthrenes exhibit promising immunomodulatory effects in various human diseases. In this study, we isolated one new dihydrophenanthrene derivative (1), two new bibenzyl-dihydrophenanthrene derivatives (2, 3) along with 12 known compounds (4–15) from the methanol extract of Calanthe cardioglossa. These compounds were identified by using physicochemical analyses and spectroscopic methods. The three new compounds possess enantiomeric forms, and their configurations were determined by comparing the experimental electronic circular dichroism (ECD) spectra to data from the literature. The immunomodulatory activity of the isolated compounds was assessed in THP-1 monocytes and human peripheral blood mononuclear cells (PBMCs) derived from multiple sclerosis (MS) patients. Notably, five of the isolated compounds significantly reduced the TNF-α levels in LPS-stimulated THP-1 monocytes. Furthermore, calancardin B (2) exhibited a significant reduction in TNF-α levels in both THP-1 monocytes and CD14⁺ monocytes from MS PBMCs.

A structurally novel metabolite, fatuamide A (1), was discovered from a laboratory cultured strain of the marine cyanobacterium Leptolyngbya sp., collected from Faga’itua Bay, American Samoa. A bioassay-guided approach using NCI-H460 human lung cancer cells directed the isolation of fatuamide A, which was obtained from the most cytotoxic fraction. The planar structure of fatuamide A was elucidated by integrated NMR and MS/MS analysis, and a combination of bioinformatic and computational approaches was used to deduce the absolute configuration at its eight stereocenters. A putative hybrid PKS/NRPS biosynthetic gene cluster responsible for fatuamide A production was identified from the sequenced genomic DNA of the cultured cyanobacterium. The biosynthetic gene cluster possessed elements that suggested fatuamide A binds metals, and this metallophore property was demonstrated by native metabolomics and indicated a preference for binding copper. The producing strain was found to be highly resistant to toxicity from elevated copper concentrations in culture media.

Ten new resin glycosides, controlins I–X (1–10), were isolated from the seeds of Convolvulus tricolor. Their structures were established by spectroscopic analysis as well as by chemical means. Compounds were identified as glycosidic acid methyl esters, considered as artifacts generated via transesterification with MeOH from natural resin glycosides. Compound 1 is the first nonasaccharide resin glycoside, while compounds 2–7 are rare octasaccharide resin glycosides. Compounds 5, 6, and 8 could inhibit the nitric oxide production in lipopolysaccharide-induced BV-2 cells, while compounds 3, 5, and 7 exhibited neuroprotective effects on H₂O₂-induced damage in PC12 cells. Compounds 6 and 7 could dose-dependently alleviate the dyskinesia in the UM0001 strain of Caenorhabditis elegans, a double transgenic line of Aβ and pro-aggregation tau, suggesting an anti-Alzheimer’s activity, reported for resin glycosides for the first time.