Phytochemistry最新文献

From the root barks of a Central African tree Millettia dubia De Wild. (Fabaceae), ten previously undescribed oleanane-type glycosides were isolated by various chromatographic protocols. Their structures were elucidated by spectroscopic methods, mainly 2D NMR experiments and mass spectrometry, as mono- and bidesmosidic glycosides of mesembryanthemoidigenic acid, hederagenin and oleanolic acid. The stimulation of the sweet taste receptor TAS1R2/TAS1R3 by these glycosides was evaluated, and structure/activity relationships were proposed. Two of them showed an agonist effect on TAS1R2/TAS1R3.

Glycosyltransferases catalyze the transfer of a glycoside group to a wide range of acceptor compounds to produce glycoconjugates with diverse biological and pharmacological activities. The present work reports the identification and biochemical characterization of Nicotiana tabacum UGT89A2 glycosyltransferase (NtUGT89A2). The enzyme is a monomer in solution that catalyzes the O-β-glucosylation of di- and tri-hydroxylated and chlorinated derivatives of benzoic acid. NtUGT89A2 has a preference for 2,5-dihydroxybenzoic acid (2,5-DHBA) over 2,3-dihydroxybenzoic acid (2,3-DHBA) and 2,4-dihydroxybenzoic acid (2,4-DHBA). Other substrates that can be used by NtUGT89A2 include 3,4,5-trihydroxybenzoic acid and chlorinated derivatives such as 2-chloro-5-hydroxybenzoic acid (2-Cl-5-HBA). The substrates of NtUGT89A2 were identified by thermal stability experiments, where we observed a maximum increase of the thermal denaturation midpoint (T_m) of 10 °C in the presence of 2,5-DHBA and UDP-glucose. On the other hand, the highest specific activity was obtained with 2,5-DHBA (225 ± 1.7 nkat/mg). Further characterization revealed that the enzyme has a micromolar affinity for its substrates. Notably, the enzyme retains full activity after incubation at 70 °C for 1 h. These results provide a basis for future functional and structural studies of NtUGT89A2.

Five undescribed monoterpene-chalcone conjugates (1-5), one undescribed hypothetical precursor of diarylheptanoid (6), two undescribed diarylheptanoids (7–8), and fourteen known compounds (9–22) were isolated from the seeds of Alpinia katsumadai. Their structures were elucidated through the interpretation of HRESIMS, NMR, ECD, and X-ray diffraction data. MTT assays on human cancer cell lines (HepG2, A549, SGC7901, and SW480) revealed that compounds 3–8, 11, and 13 exhibited broad-spectrum antiproliferative activities with IC₅₀ values ranging from 3.59 to 21.78 μM. B cell lymphoma 2 was predicted as the target of sumadain C (11) by network pharmacology and verified by homogeneous time-resolved fluorescence assay and molecular docking.

The genus Penicillium has provided us with the household antibiotic penicillin and the well-known lipid-lowering agent mevastatin. The strain Penicillium sp. SZ-1 was found to grow vigorously in an intact Pinus koraiensis seed, it is inferred that the strain may develop unique mechanisms associated with the biosynthesis of rare metabolites. Further fermentation of the strain on solid rice medium yielded thirteen undescribed compounds, including three andrastin-type meroterpenoids (1−3), two α-pyrone polyketides (4 and 5), and eight sesquicarane derivatives (6−13), along with seven known compounds (14−20). Their structures were determined by detailed analysis of the spectroscopic and spectrometric data (NMR and HRESIMS), in addition to comparisons of the experimental and calculated ECD data for absolute configurational assignments. The hemiacetal moiety in compounds 1 and 2 and the 3α-hydroxy group in compound 3 were rarely found in the andrastin-type meroterpenoid family. The sesquicaranes belong to a small group of sesquiterpenoid that are rarely reported. Bioassay study showed that compound 1 exhibited inhibitory effects against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 with MIC values of 64 and 32 μg/mL, respectively. In addition, compounds 1 and 3 displayed weak DPPH radical scavenging activities. The andrastins and sesquicaranes in this study enriched the structural diversity of these classes of terpenoids. Of note, this study is the first report on the metabolites of a fungus isolated from P. koraiensis seed.

Seven undescribed 3,4-secolanostane triterpenoids, daldiconoids A-G (1–7), were isolated from the fruiting bodies of Daldinia concentrica. Daldiconoid A (1) was a highly modified 4,6,28,29-tetranorlanostane triterpenoid alkaloid featuring an unusual δ-lactam fused with a flanking cyclopentenone architecture. Their structures were determined by spectroscopic data, NMR calculations coupled with the DP4+ analysis, X-ray single-crystal diffraction, and chemical transformation. The plausible biosynthetic pathway for 1 was proposed. Compounds 1, 2, and 4–6 inhibited the expressions of IL-1β, IL-6, and TNF-α in lipopolysaccharide stimulated RAW264.7 cells at a concentration of 10 μM. Mechanistically, Compounds 1 and 2 blocked the JAK2/STAT3 signaling pathway induced by lipopolysaccharide.

Five undescribed atranones, namely atranones V–Z (1–5), three undescribed dolabellane-type diterpenoids, namely stachatranones D–F (7–9), together with four known congeners (6 and 10–12), were obtained from a coral-associated strain of the toxigenic fungus Stachybotrys chartarum. Their structures were elucidated via extensive spectroscopic analyses, mainly including the HRESIMS and NMR data, single-crystal X-ray diffraction analysis, electronic circular dichroism calculation, and [Mo₂(OAc)₄] induced circular dichroism spectrum. The cardiomyocyte protective activity assay revealed that compound 9 significantly ameliorated cold ischemic injury at 24 h post cold ischemia (CI) in a dose-dependent manner. Moreover, compound 9 prevented CI induced dephosphorylation of phosphatidylinositol-3-kinase and RAC-α serine/threonine-protein kinase at 12 h post CI in a dose-dependent manner. In this work, the undescribed compound 9 could significantly protect cardiomyocytes against cold ischemic injury, highlighting the promising potential to be designed and developed as a novel cardioprotectant in heart transplant medicine.

Three previously undescribed and sixteen known alkaloids were bioguidedly isolated from the bulbs of Narcissus tazetta subsp. chinensis (M.Roem.) Masamura & Yanagih. The structures were elucidated by spectroscopic data, including HRESIMS, NMR, and ECD. Eleven of the isolated alkaloids exhibited immunosuppressive activity on the proliferation of human T cells. (+)-Narciclasine (18) showed the most significantly suppressive activity with an IC₅₀ value of 14 ± 5 nM. In vitro, (+)-narciclasine (18) blocked NF-κB signal transduction, but did not affect PI3K/AKT signal transduction. What was more, (+)-narciclasine significantly reduced ALT and AST levels and alleviated liver damage induced by ConA in AIH mouse model.

One previously undescribed xanthanolide sesquiterpene dimer pungiolide P (1), possessing an unprecedented scaffold with a 5/7/5/7/5 ring system skeleton and its intermediate pungiolide Q (2), ten xanthanolide sesquiterpenes (3–12), two eudesmene sesquiterpene derivatives (13–14), one phenylpropionic acid derivative (15), together with eleven known compounds (16–26) were obtained from the fruits of Xanthium italicum Moretti. A possible biosynthetic pathway for pungiolide P (1) was also proposed, which was supported by its bio-synthetic intermediate (2). Compounds 1, 4–5, 18–21, and 25 exhibited cytotoxic activity against a variety of human cancer cell lines. Furthermore, compounds 1, 4–5, could cause blockage of the cell cycle in the G2/M phase and induce apoptosis in H460 cells. Notably, pungiolide P (1) exhibited significantly superior cytotoxicity compared to previously reported compounds, providing valuable insights for natural anti-tumor sources.

Rhododendron dauricum L. is a perennial herb belonging to the genus Rhododendron, commonly utilized in formulations for treating coughs and bronchitis, as well as in herbal teas for enhancing immunity and preventing tracheitis. In this study, fifteen previously undescribed chromene meroterpenoids (1a/1b-4a/4b, 5–8, 9b, 10a, 11b), along with twenty-one known compounds were isolated from the dried twigs and leaves of Rhododendron dauricum L. Of these, (−)-rhodonoid E (9b), (+)-confluentin (10a), and (−)-rubiginosin D (11b) were separated for the first time by chiral HPLC separation. The elucidation of their structures, including absolute configurations, was achieved through a combination of techniques such as NMR, HRESIMS, modified Mosher's method and quantum-chemical calculation of electronic circular dichroism (ECD) spectra. Seven pairs of enantiomers, compounds 1a/1b-4a/4b and 9a/9b-11a/11b, were initially obtained in a racemic manner and were further separated by chiral HPLC preparation. The biological assessment of these compounds against NO production was conducted in the LPS-induced RAW264.7 macrophage cells model. Compounds 9a, 9b, and 11a displayed inhibitory rates exceeding 80%, with IC₅₀ values ranging from 8.69 ± 0.94 to 13.01 ± 1.11 μM. A preliminary examination of the structure-activity relationship (SAR) for these isolates indicated that chromene meroterpenoids with α, β-unsaturated ketone carbonyl and Δ¹²⁽¹³⁾ double bond functionalities exhibited enhanced anti-inflammatory properties.

Seven previously undescribed flavonol glycosides including four rare flavonol glycoside cyclodimers, dicyclopaliosides A-C (1-3) with truxinate type and dicyclopalioside D (4) with truxillate type, as well as three kaempferol glycoside derivatives cyclopaliosides A-C (5–7), were obtained from the leaves of Cyclocarya paliurus. Their structures were elucidated by extensive spectroscopic methods and chemical analyses. All compounds were evaluated for their inhibitory α-glucosidase activities. Among them, compounds 1–4 display strong inhibitory activities with IC₅₀ values of 82.76 ± 1.41, 62.70 ± 4.00, 443.35 ± 16.48, and 6.31 ± 0.88 nM, respectively, while compounds 5–7 showed moderate activities with IC₅₀ values of 4.91 ± 0.75, 3.64 ± 0.68, and 5.32 ± 0.53 μΜ, respectively. The structure-activity relationship analysis assumed that the cyclobutane cores likely contribute to the enhancement of α-glucosidase inhibitory activities of dimers. Also, the interaction mechanism between flavonol glycoside dimers and α-glucosidase were explored by the enzyme kinetic assay, indicating that compounds 1–3 exhibited mixed-type inhibition, while 4 showed uncompetitive inhibition. Additionally, the active compounds have also undergone molecular docking evaluation.