Journal of Natural Products 最新文献

An investigation of a cytotoxic MeOH extract of the branches of Beilschmiedia yunnanensis, collected in Vietnam, led to the isolation of four new compounds (1–4). Two of these, isolated from a CHCl₃-soluble partition, were characterized as the furofuran-type neolignans, beilschmiedianins A (1)[(7R,7′R,8S,8′S,8″R)-4′,4″,9′′-trihydroxy-3,5,3′,3′′-tetramethoxy-4,8′′-oxy-7,9′:7′9-diepoxy-8,8′-sesquilignan-7′′-one)] and B (2) [(7R,7′R,7″R,8S,8′S,8″R)-9″-feruloyl-4′,4′′-dihydroxy-3,5,3′,3′′-tetramethoxy-4,8″-oxy-7,9′:7′,9-diepoxy-8,8′-dilignan-7″-ol]. In turn, the flavonoid glycosides 3 and 4 were obtained from an EtOAc-soluble partition and were assigned as (2R,3R)-dihydrokaempferol-5-O-β-l-arabinosyl-(2→1)-α-l-rhamnopyranoside and (2R,3R)-dihydrokaempferol-5-O-β-l-arabinopyranoside, respectively. The structures of these new compounds were determined using a combination of spectroscopic and spectrometric methods. Additionally, the known dilignan, (−)-9,9′-O-diferuloylsecoisolariciresinol (5), showed selective cytotoxicity against the OVCAR3 ovarian cancer cell line, with an IC₅₀ value of 0.51 μM. Mechanistic studies showed that compound 5 increased the cPARP levels and decreased the expression of BCL-2 in OVCAR3 cells.

Sarcglabtenes A–G (1–7), seven lindenane-based sesquiterpenoid hetero-oligomers with six unprecedented skeletons, along with five new biosynthetic analogues sarcglabtenes H–L (8–12), were isolated from Sarcandra glabra. Their structures including absolute configurations were comprehensively elucidated using HR-MS, NMR, ECD, and single crystal X-ray diffraction. Structurally, sarcglabtenes A–G are lindenane hetero-oligomers including a geranyl homogentisic acid (1/2), geranylgeranyl p-toluquinone (3/4), germarane (5), campholenal (6/7) derivatives, for which plausible biosynthesis pathways are also proposed. In bioassays, 1–4 exhibited cytotoxic activity against five cancer cell lines, and in particular, 4 acted as extracellular-regulated protein kinase (Erk) inhibitor of the MAPK signaling pathway involved in apoptosis.

Thirteen new 3,4-seco-tirucallane triterpenoids (1–11, 15, 16), along with one new 2,3-seco-tirucallane triterpenoid (17), one new 3,4-seco-29-nor-tirucallane triterpenoid (12), one new 3,4-seco-28,29-dinor-tirucallane triterpenoid (13), and a known tirucallane analogue (14) were isolated from leaves of Dysoxylum gotadhora. These triterpenoids were structurally determined by spectroscopic methods, including HRESIMS, NMR spectroscopic analyses, single-crystal X-ray diffraction, and ECD data. The cytotoxicity evaluation revealed that compounds 4 and 11 exhibited moderate activity against HCT-116 and DLD-1 cell lines with IC₅₀ values ranging from 3.7 to 4.4 μM. The Annexin V-PE/7-AAD staining assay indicated that both 4 and 11 induced apoptosis in a concentration-dependent manner. Further studies showed that compounds 6, 9, 10, and 17 exhibited suppression effects on NO production in LPS-induced RAW 264.7 cells, with IC₅₀ values ranging from 17.1 ± 3.3 to 49.8 ± 6.5 μM.

The way immune cells attack pathogenic microorganisms might trigger pathogens to produce compounds that promote their survival. Based on this idea, we constructed a coculture system of pathogenic fungi and immune cells and isolated fumigatinolactone (1) as a new natural product by coculture of Aspergillus fumigatus IFM 60237 with RAW264 mouse macrophage-like cells. Fumigatinolactone (1) was produced via a nonenzymatic coupling reaction between fumigatin (4) and a new type of intermediate fumarylazlactone (5). An investigation of the interaction mechanism between the fungi and cells revealed that the survival interaction between pathogen and immune cells played key roles. Surprisingly, fungi showed a response to nitric oxide (NO), which was produced by macrophages, resulting in the production of 4. In addition, an iron starvation condition triggered the production of 5. Finally, 1 was obtained by these two mechanisms. Furthermore, compounds 1–4, particularly 4, showed inhibition of NO production from RAW264, which might be a defense action for macrophage by fungi. This is the first example of elucidation of interaction mechanisms between pathogen and immune cells for activation of silent genes to produce a new compound. These findings suggest that host–pathogen survival interaction may increase the production of secondary metabolites from fungi.

Ants typically demonstrate a high level of complex social behavior that is largely mediated by chemical communication. In recent years, the Clonal raider ant Ooceraea biroi has become a promising model system for the study of social behavior in ants. Here we report the profile of extracted volatiles from O. biroi and, following detection of an α-homofarnesene as the major component, unambiguously confirm its structural identity as (3Z,6E)-14-methyl-α-farnesene through preparative stereoselective total synthesis.

The first asymmetric total synthesis of (+)-karanone, a key aroma compound in high-grade agarwood (“Kyara”), was accomplished in 17 steps from 4-penten-2-ol. The key stereocenters at C7, C4, and C5 were introduced via asymmetric aldol condensation and Ireland–Claisen rearrangement. The oxygen-functional group at C8 was formed through oxidative rearrangement, and the bicyclic core of (+)-karanone was constructed by ring-closing metathesis. Two related compounds, namely (+)-4-epi-karanone and (+)-warburgiadione, were also synthesized. Studies of the structure–odor relationship among (+)-karanone, (+)-4-epi-karanone, and (+)-warburgiadione were also performed.

Kahalalides were originally isolated from the marine mollusk Elysia rufescens and its green algal diet Bryopsis sp., but the true producer was revealed as the obligate bacterial symbiont Candidatus Endobryopsis kahalalidefaciens, residing within Bryopsis sp. The most notable is kahalalide F, a broad-spectrum antitumor depsipeptide that entered the clinic but failed from lack of efficacy. We have isolated three new glycosylated analogues of kahalalide F, termed dapalides A–C (1–3), from a marine cyanobacterium, Dapis sp., collected from Guam. The planar structures were determined by extensive NMR coupled with mass spectrometry. Acid hydrolysis of 1 using amino acid analysis revealed the absolute configuration of singlet and a mixture of duplicate amino acids. Metagenomic analysis unveiled a biosynthetic gene cluster (BGC) with a nonribosomal peptide synthetase (NRPS) system and downstream glycosylation enzymes, which assisted the configurational assignment through epimerization domain analysis. The discovered BGC, termed dap, was assigned to a high-quality metagenome-assembled genome of the Dapis sp. Dapalide A (1) was subjected to phenotypic bioassays and exhibited weak anticancer cytotoxicity. This discovery expands the chemical diversity of the kahalalide F family, suggests their broad ecological role across diverse organisms, and presents an intriguing case of natural product biosynthesis evolution.

Diffuse pleural mesothelioma (DPM) is a rare but aggressive late-onset cancer. A high-throughput screen of a natural product fraction library identified fractions derived from an aqueous extract of Sinularia sp. soft coral that reduced the viability of DPM cell lines. Bioassay-guided fractionation of the parent extract resulted in the identification of 13 cembrane diterpenoids, including nine new natural products sinulariolones B–J (1–4, and 7–11), as the active principles. The planar structures of the new compounds were established by the analysis of NMR spectroscopic and MS spectrometric data. Their relative and absolute configurations were determined using a combined approach, including NOESY interpretation, modified Mosher’s method, ECD simulation, and single-crystal X-ray diffraction. All pure metabolites were tested for their effects on the viability of the DPM cell lines, and compounds 2, 3, 8, and 9 demonstrated low micromolar potency against these cancer cell lines.

Natural products exhibiting selective or preferential antifungal activity against fission yeast over budding yeast might contribute greatly to new discoveries in the life sciences and new drug and agrochemical development. However, it is difficult to discover new drug and agrochemical candidates in the fission yeast screening system due to its low drug sensitivity. In this study, we constructed a new antifungal drug and agrochemical candidate screening platform using a drug-hypersensitive fission yeast strain. We executed antifungal activity profiling of our natural compound and microbial libraries against drug-hypersensitive fission yeast and multidrug-sensitive budding yeast. Ultimately, we identified MS-347a as a promising agrochemical candidate due to its excellent activity against the rice blast fungus.

In an antifungal screening of extracts from microbial strains isolated from gypsum outcrops in Granada, Spain, four new cyclic lipopeptides, glycinocins E–H (1–4), were identified from Streptomyces sp. CA-297274 and exhibited potent activity against Zymoseptoria tritici, the causal agent of septoria tritici blotch of wheat. Isolation and structure elucidation performed using HR-MS/MS, 1D and 2D NMR, and Marfey’s analyses, revealed that structures contained an Asp-Gly-Asp-Gly motif in the peptide scaffold, typical of calcium-dependent antibiotics. Genome sequencing and bioinformatic analysis of the strain uncovered a biosynthetic gene cluster consistent with the production of these compounds and helped to correct the absolute configuration determined by Marfey’s analysis of some amino acid residues. The isolated metabolites displayed notable antifungal activity against Z. tritici, with minimum inhibitory concentration values in the micromolar range (Compound 4, 9.5 μM), and calcium-dependent antibacterial activity against methicillin-resistant Staphylococcus aureus (5.2 μM for 4) and vancomycin-resistant Enterococcus faecium (3.0 μM for 4), as anticipated by their structural analysis. Glycinocins E–H displayed no cytotoxicity against the human liver cancer cell line HepG2. These findings expand the chemical diversity of calcium-dependent antibiotics and highlight the ecological and therapeutic potential of extremophile-derived actinomycetes as a source of novel bioactive compounds.