Journal of Natural Products 最新文献

An azaphilone, 6,7-iso-felinone A (2), was isolated from Diaporthales sp. KT3922 along with the known felinone A (1). While compound 2 exhibited weak Cotton effects, its naphthoate derivative (2a) displayed pronounced Cotton effects, enabling the determination of its absolute configuration through electronic circular dichroism (ECD) spectral analysis. Interestingly, the spectroscopically derived relative structure of compound 2 proved identical to previously reported hypoillexidiol (3) and xylariphilone (4). However, substantial differences in ¹H nuclear magnetic resonance data among these compounds warranted structural reinvestigation of the entire series, including the structurally related fungal metabolites, fusaraisochromenone (5) and aspergillusone C (6). Comparative analysis revealed identical relative configurations of compounds 1, 3, 4, and 5. Furthermore, compounds 1 and 3 were determined to have an identical absolute configuration, whereas the absolute configuration of compound 4 remained inconclusive due to a significant mismatch in its ECD spectral profile compared to compound 1. Compound 5 was identified as the enantiomer of compounds 1 and 3. Additionally, we discussed the stereochemistry of the 6,7-cis-diol isomer, aspergillusone C (6).

Seven new sesquiterpene hydroquinone/quinone (SQ) meroterpenoids, cinerols L-R (1-7), along with four known analogues (8-11), were identified from a marine sponge, Dysidea cinerea, collected from the shore of the Xisha Islands in the South China Sea. The structures of 1-7 were established by the analysis of NMR, high-resolution MS, and comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Cinerol L (1) is particularly noteworthy, as it features a 5H-pyrrolo[1,2a]-benzimidazole moiety modified by an ethyl sulfonate, while cinerols N (3) and O (4) possess a unique acetyl-substituted hydroquinone moiety. Cinerols L-R (1-7) were evaluated for their inhibitory activity against inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and prostaglandin E2 (PGE₂) with IC₅₀ values of 5-20 μM in lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages. Furthermore, the potent inhibitory activity on inflammatory cytokines of 4 prompted us to evaluate its effect on the nuclear factor-κB (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway, a critical pathway that contributes to the inflammatory responses. Cinerol O (4) was unveiled to inhibit cyclooxygenase-2 (COX-2) expression and the production of inflammatory cytokines via suppressing the expression of NF-κB and MAPKs in LPS-induced RAW 264.7 macrophages.

Twelve new isocoumarins, spegazmarins A-L (1-12), including nine novel dimeric derivatives (1-9), three monomeric derivatives (10-12), as well as eight known ones (13-20), were isolated from the endophytic fungus Spegazzinia sp. MDCW-573. Their structures were elucidated by analysis of NMR, X-ray crystallography, and ECD data. Notably, the dimeric isocoumarins (1-9) possess a unique linkage, where the phenyl of one monomer is connected to the lactone of another. The methods for determining the configurations of both the monomeric and dimeric isocoumarins within this class were proposed, leading to the correction of the configurations of two previously reported isocoumarins. The isolated compounds inhibited Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, with MIC values of 1 to 64 μg/mL. Compounds 5, 6, and 12 significantly promoted the growth of zebrafish intersegmental vessels at concentrations of 10, 20, and 40 μM, respectively.

Recent analyses of genome data indicate that members of the cyanobacterial order Pleurocapsales show tremendous potential for natural product discovery. However, only a few compounds have been reported from this order. Here, we report the isolation of hyellamide (1), a glycosylated N-acyl tyrosine-derived eneamide, from the pleurocapsalean cyanobacterium Hyella patelloides LEGE 07179. The putative biosynthetic gene cluster for 1 was identified in the genome of the producing organism and a biosynthetic proposal is presented. This work sheds light on the chemistry of the Pleurocapsales and expands the chemical repertoire of cyanobacterial natural products to include N-acyl tyrosine-derived molecules.

Menominin A (1) and B (2), two cyclodepsipeptides containing a 3,8-dihydroxy-2-methyltetradecanoic acid residue, were isolated from the freshwater sponge-associated cyanobacterium, Nostoc sp. UIC 10607, using bioactivity-guided and spectroscopic approaches. The planar structures of 1 and 2 were established using HRESIMS and one- and two-dimensional NMR experiments. Comparative genomic analysis revealed unique differences in the putative menominin biosynthetic gene cluster compared to that of the closely related cyanobacterial cyclic lipodepsipeptide, hapalosin, assisting in structure elucidation and highlighting the structural diversity of this class of compounds. Configuration assignments were determined using a combination of J-based configuration analysis, chiral HPLC, modified Mosher's ester analysis, and DFT calculations. Menominin A and B demonstrate antiproliferative bioactivity against the high-grade serous ovarian cancer cell line OVCAR3 (IC₅₀ = 3.1 (1) and 2.4 μM (2)). Menominin A and B are the first reported secondary metabolites from a freshwater sponge-associated cyanobacterium, underscoring the potential of freshwater sponges as a microbial culture source in natural product discovery.

LaeA is a putative nuclear methyltransferase protein that epigenetically influences secondary metabolite production in fungi. LaeA has drawn attention as one of the promising approaches to activate fungal chemical production, and the laeA gene has been introduced into some fungal strains with the aim of producing secondary metabolic changes mainly based on the evaluation of mycotoxicity. However, these studies were applied for limited fungal species, and its utility and versatility for broad fungal species remained unclear. In this study, 47 strains were selected composed of three different genera, Pochonia spp., Gamszarea kalimantanensis, and Lecanicillium spp., which have never been modified with the laeA gene. We obtained a total of 125 mutants with laeA genes for our fungal strain library. The chemical productivity and the biological activity of the library were analyzed, and two natural products, radicicol (1) and sch210972 (2), were isolated in more than 10-fold the yield of the parent strains.

Thirty compounds including 13 new phenolic glycosides (1-6, 9-15) and 17 known aromatic compounds and aromatic glycosides (7-8, 16-30) were isolated from the roots of Wrightia pubescens. The structures of the new phenolic glycosides were established by extensive NMR spectroscopic data analysis as well as chemical derivatization method. The isolated compounds were evaluated for their hepatoprotective activities using cell model of acetaminophen (APAP)-induced HepG2 cells. The results indicated that phenolic glycosides (2, 4, 5, 7, 8, 11, 13) pretreatment enhanced the cells viability and reduced the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT). The hepatoprotective mechanism of a representative new compound, wrightioside D (4), was further investigated. Compound 4 exhibited hepatoprotective effects via reducing oxidative stress by attenuating ROS formation and inhibiting apoptosis in APAP-treated HepG2 cells.

Two novel spiro aromatic polyketides, (+)- and (-)-feionemycin A (1), along with four atypical angucyclinones named as chromonemycins A-D (2-5), were discovered through heterologous expression of a type II polyketide gene cluster, within which one previously characterized flavoprotein monooxygenase was deactivated. Among those structures, compound 1 features an unprecedented oxaspiro[5.4]undecane architecture, and compounds 2-5 represent novel atypical angucyclinone variants derived from unusual cyclization of the polyketide chains. The structures and absolute configurations were elucidated by NMR, MS, single-crystal X-ray diffraction, theoretical NMR calculations, DP4+ probability analysis, and ECD analyses. (+)-1 showed cytotoxic activity against NCI-H446, with an IC₅₀ value of 2.26 μM.

This study describes the first and efficient syntheses of naturally occurring ugonins L (1a), S (2a, 2b), U (3), and Z (4). Naturally occurring ugonin S has two stereoisomers. On the basis of their NMR and specific rotation data, the absolute configuration of trans-ugonin L (1a) was determined as 10R,11R, while the absolute configurations of trans-ugonin S (2a) and cis-ugonin S (2b) were determined to be 10R,11R and 10R,11S, respectively. The naturally occurring cis-ugonin U (3) presented the 10S,11R configuration. The naturally occurring cis-ugonin Z (4) was suggested to have a 10S,11R configuration. Four isomers of compound 2 and two isomers of compound 3 showed moderate cytotoxic activities against the CEM and H460 human cancer cell lines.

Four chromene dimers, panusimilins A-D (1-4) (racemic mixtures), and two previously undescribed chromanes (5a/5b and 6a/6b) were isolated from cultures of basidiomycete Panus similis TBRC-BCC 52578. Interestingly, synthetic compounds closely related to panusimilins A-C (1-3) were previously reported, which were produced by Lewis acid promoted dimerization of a plant-derived chromene, precocene II. In the present study, panusimilins were isolated from the culture broth extract of the fungus P. similis. The chromane monomers were shown to be a non-racemic mixture of enantiomers, and their absolute configurations were elucidated by conversion to Mosher ester derivatives. The isolated compounds were evaluated for their cytotoxic activities. Among them, 2,2-dimethyl-3,4,6-trihydroxychromane (6a/6b) showed selective activity to NCI-H187 cells (IC₅₀ 9.1 μM). On the other hand, panusimilin B (2) exhibited antioxidant activity in the DPPH radical scavenging assay (IC₅₀ 66 μM).