Phytochemistry最新文献

An extensive phytochemical investigation on the EtOAc-soluble fraction of the 90% MeOH extract from the twigs and needles of the ‘vulnerable’ Chinese endemic conifer Tsuga forrestii (Forrest's hemlock) led to the isolation and characterization of 50 structurally diverse diterpenoids, including 15 unreported C-18 carboxylated ones (tsugaforrestiacids A−O, 1−15, resp.). Among them, compounds 1−7 are abieten-18-oic acids, compound 8 is an abieten-18-succinate, and compounds 10−12 are podocarpen-18-oic acids, whereas compounds 13−15 are pimarane-type, isopimarane-type, and totarane-type diterpenoid acids, respectively. Their structures and absolute configurations were determined by a combination of spectroscopic methods, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism (ECD) data, and single crystal X-ray diffraction analyses. All the isolates were evaluated for their inhibitory activities against the ATP-citrate lyase (ACL), a key enzyme in cellular metabolism. Tsugaforrestiacids E (5) and H (8) were found to have significant inhibitory effects against ACL, with IC₅₀ values of 5.3 and 6.2 μM, respectively. The interactions of the bioactive molecules with the ACL enzyme were examined by molecular docking studies. The isolated diterpenoids also provide chemotaxonomic evidence to support the delimitation of Tsuga from its closest sister group (Nothotsuga). The above findings highlight the importance of protecting plant species with unique and diverse secondary metabolites, which may be potential sources of new therapeutic agents for the treating ACL-associated diseases.

Eight previously undescribed sesquiterpene lactones (1–8), together with six known ones (9–14) were isolated from the aerial parts of Tithonia diversifolia (Hemsl.) A. Gray. The absolute configurations of these compounds were elucidated using HRMS, NMR spectroscopy, optical rotation measurements, X-ray crystallography, and ECD. Among them, sesquiterpene lactones 2–4 share a unique carbon skeleton with a rare C-3/C-4 ring-opened structure. Compounds 1 and 8 showed moderate inhibitory effects toward CT26 murine colon carcinoma cells by promoting lipid ROS production, highlighting their potential as ferroptosis inducers.

Fourteen undescribed nitrogenous merosesquiterpenoids, purpurols A−D (1–4) and puraminones A−J (5–14), along with three known related compounds (15–17) were isolated from the sponge Pseudoceratina purpurea collected in the South China Sea. Their structures and absolute configurations were unambiguously elucidated by a combination of spectroscopic data, X-ray diffraction analysis, electronic circular dichroism calculations, and chemical derivatization. Purpurols A−D (1–4) incorporated nitrogenous heterocycles, compounds 1 and 2 feature an unusual benzothiazole ring, while 3 and 4 feature benzoxazole ring. Puraminones A−J (5–14) represent sesquiterpenoid aminoquinones with different amine and amino acid side chains at C-20. Additionally, twenty unreported sesquiterpenoid aminoquinone analogues were obtained through chemical derivatization. It is worth noting that all compounds are featured with unusual rearranged 4,9-friedodrimane subunit. In the bioassays, purpurols A and B showed weak anti-inflammation in zebrafish, as well as some compounds showed activities against tumor cells, therefore, preliminary structure–cytotoxicity relationships are also discussed.

Anemone vitifolia is a small herb found in Asia that is used to treat a range of diseases in Chinese traditional medicine. GNPS-based molecular networking of an Anemone vitifolia specimen revealed the presence of a network containing numerous ions indicating the presence of lignans, several of which suggested that there might be previously undescribed compounds in the extract. Fractionation of the organic extract yielded five undescribed lignans, the vitifolignans, together with one known. The structures were identified based on extensive spectroscopic data analysis (NMR, HR-ESI-MS, and UV), coupling constant calculation and comparison with reported data. Their absolute configurations were determined by comparison of experimental ECD spectra with calculated spectra. Compounds 4/5 showed weak inhibition of LPS-induced NO production in mouse mononuclear macrophages.

Seven undescribed benzoate glycosides (1−7) and five known ones (8−12) were isolated from the rhizomes of Gentiana scabra Bge. Their structures were characterized by comprehensive NMR and MS spectroscopic data analysis. The lipid-lowering effects of these compounds were evaluated by measuring the triglyceride (TG) contents and intracellular lipid droplets (LDs) in oleic acid (OA)-treated HepG2 cells. The results showed that compounds 1, 5, 7, and 11 significantly reduced the TG content at 20 μM, and the Bodipy staining displayed that OA enhanced the levels of LDs in the cell, while these compounds reversed the lipid accumulation caused by OA. These findings provide a basis for further development and utilization of G. scabra as a natural source of potential lipid-lowering agents.

Lappanolides A−N (1–14), 14 undescribed sesquiterpenoids, along with 23 known ones (15–37), were isolated from the roots of Saussurea costus, which were primarily categorized into eudesmane, guaiane, and germacrane types. Lappanolide A (1) possessed an unprecedented pseudo-disesquiterpenoids. Their structures and absolute configurations were established using physical data analyses (HRESIMS, IR, 1D and 2D NMR) and ECD calculations. All isolated compounds were tested for anti-hepatitis B virus (anti-HBV) activity. Ten compounds (1, 9, 11, 12, 19, 22, 28, 29, 31, and 36) exhibited activities against HBsAg secretions as determined by ELISA assay, with IC₅₀ values ranging from 5.2 to 45.7 μM. In particular, compounds 28 and 29 showed inhibition of HBsAg secretion with IC₅₀ values of 5.28 and 5.30 μM, and CC₅₀ values of 9.85 and 6.37 μM, respectively, though they all exhibited low selectivity. Several compounds displayed cytotoxicity in the MTT assay. Among them, compound 28 was the most notable and was chosen for further study using flow cytometry. The result showed that it significantly induced HepG2 cell arrest in the S phase and induced apoptosis.

Artemisia annua L. (“Qinghao” in Chinese) is a famous traditional Chinese medicinal herb and has been used to treat malaria and various tumors. Our preliminary screening indicated that the EtOAc extract of A. annua manifested activity against HepG2, Huh7, and SK-Hep-1 cell lines with inhibitory ratios of 53.2%, 52.1%, and 59.6% at 200 μg/mL, respectively. Bioassay-guided isolation of A. annua afforded 14 unusual cadinane-involved sesquiterpenoid dimers, artemannuins A‒N (1–14), of which the structures were elucidated by extensive spectral analyses, ECD calculations, and single-crystal X-ray diffraction. Structurally, these compounds were classified into five different types based on the coupled modes of two monomeric sesquiterpenoids. Among them, compounds 1–9 represented the first examples of sesquiterpenoid dimers formed via the C-3‒C-3′ single bond of two 5(4 → 3)-abeo-cadinane sesquiterpenoid monomers, while compounds 13 and 14 were dimers fused by cadinane and humulane sesquiterpenoids via an ester bond. Methylated derivatives of 1, 4, 6, and 8 showed antihepatoma activity against HepG2, Huh7, and SK-Hep-1 cell lines with IC₅₀ values ranging from 30.5 to 57.2 μM.

Eighteen compounds including eleven previously undescribed diterpenes were isolated from the leaves of Croton mangelong. The structures were determined by HRESIMS, IR, NMR, X-ray diffraction and ECD spectroscopic analysis. All isolates were assayed for their anti-hyperglycemic activities in insulin resistance (IR) 3T3-L1 adipocytes, and compound 4 was tested for its anti-diabetic activity in vivo. Results suggested compound 4 could effectively reduce blood glucose level in diabetic SD rats in a dose of 30 mg/kg.

Acanthopanacis cortex (the dried root bark of Acanthopanax gracilistylus W. W. Smith) has been used for the treatment of rheumatic diseases in China for over 2000 years. Four previously undescribed lignans (1–4) and 12 known lignans (5–16) were isolated from Acanthopanacis cortex. In this study, the inhibitory activities of compounds 1–16 against neutrophil elastase (NE), cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) are reported. The results show that compounds 1–16 exhibit weak inhibitory activities against NE and COX-1. However, compounds 2, 6–8 and 13–16 demonstrate better COX-2 inhibitory effects with IC₅₀ values from 0.75 to 8.17 μΜ. These findings provide useful information for the search for natural selective COX-2 inhibitors.

From the Cynanchum wilfordii roots, 32 compounds, including 5 previously undescribed (1, 4-6, 12) and 27 known (2, 3, 7-11, 13-32) compounds, were isolated, and their structures were elucidated using NMR spectroscopic data and MS data aided by ECD calculations or the modified Mosher’s reaction. All isolates were tested for their inhibitory effects on proprotein convertase subtilisin/kexin type 9 (PCSK9) secretion. Among the isolates, compound 4, a methyl cholesterol analog, exhibited the most potent effect in reducing PCSK9 secretion, along with PCSK9 downregulation at the mRNA and protein levels via FOXO1/3 upregulation. Moreover, compound 4 attenuated statin-induced PCSK9 expression and enhanced the uptake of DiI-LDL low-density lipoprotein. Thus, compound 4 is suggested to be a potential candidate for controlling cholesterol levels.