MS/MS-based molecular networking discovery of sesquiterpenes from Carpesium abrotanoides L. with their cytotoxic and acetylcholinesterase inhibitory activity.

Employing an MS/MS-based molecular networking-guided strategy, three new eudesmane-type sesquiterpenes (1-3) and one undescribed pseudoguaianolide sesquiterpene (8), along with four known eudesmane-type sesquiterpene lactones (4-7) were extracted and purified from the herbs of Carpesium abrotanoides L. Structural elucidation encompassed comprehensive spectroscopic analysis, NMR calculations, DP4+ analysis, and ECD calculations. The cytotoxicity activity of all isolates was evaluated against two human hepatoma carcinoma cells (HepG2 and Hep3B) in vitro. It was demonstrated that compounds 2 and 4 showed moderate cytotoxic against HepG2 and Hep3B cells. Furthermore, all compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity. Particularly noteworthy is that, in comparison to the positive control, compound 1 demonstrated significant AChE inhibition with an inhibition rate of 77.86%. In addition, the inhibitory mechanism of compound 1 were investigated by in silico docking analyze and molecular dynamic simulation.

The sesquiterpenes with the COVID-19 Mpro inhibitory activity from the Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded four new sesquiterpenes including a novel skeleton (claroguaiane A, 1), two guaianolides (claroguaianes B-C, 2-3), and one eudesmanolide (claroeudesmane A, 4), together with three known sesquiterpenoids (5-7). The structures of the new compounds were elucidated by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitive activity of COVID-19 Mpro. As a result, compound 5 showed moderate activity with an IC50 value of 36.81 µM and compound 6 exhibited a potent inhibitory effect with an IC50 value of 16.58 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Four new eudesmane-type and one new eremophilane-type sesquiterpenes from the whole plant of Carpesium abrotanoides L.

The extract of the whole plant of Carpesium abrotanoides L. yielded five new sesquiterpenes including four eudesmanes (1-4) and one eremophilane (5). The new compounds were characterized by spectroscopic analysis especially 1D and 2D NMR spectroscopy and HRESIMS data. Structurally, both compounds 1 and 2 were sesquiterpene epoxides and 2 owned an epoxy group at C-4/C-15 position to form a spiro skeleton. Compounds 4 and 5 were two sesquiterpenes without lactones and 5 possessed a carboxy group in the molecule. Additionally, all the isolated compounds were preliminarily evaluated for the inhibitory activity against SARS-CoV-2 main protease. As a result, compound 2 showed moderate activity with an IC50 value of 18.79 µM, while other compounds were devoid of noticeable activity (IC50 > 50 µM).

Sesquiterpene lactone dimers from the fruit of Carpesium abrotanoides L.

Seven undescribed sesquiterpene lactone dimers (SLDs) (carpeabrodilactones A-G), one known SLD, and six known sesquiterpenes were isolated from the fruit of Carpesium abrotanoides L. Carpeabrodilactone A was a dimeric carabrane featuring a rare C-13-C-13' linkage. Carpeabrodilactones B and C are the first two SLDs to be described possessing a carabranolide unit and a guaianolide unit connected by an O-ether linkage. The structures of the SLDs were assigned based on HRESIMS, NMR analysis, 13C NMR calculation, ECD calculation, and modified Mosher's method. Four SLDs showed potent cytotoxicity against K562 and/or A549 cells, with IC50 values below 10 µM, but none inhibited protein tyrosine phosphatases at 40 µM, including PTP1B, SHP1, CD45, and TCPTP.

Sesquiterpene lactones from Carpesium abrotanoides L. and their activity in inducing protective autophagy.

Fourteen sesquiterpene lactones were isolated from the whole plant of Carpesium abrotanoides L. Their structures were determined on the basis of comprehensive spectroscopic data analysis. All compounds were screened for their cytotoxic activity, and compound 6 showed the strongest activity (IC50 2.73 - 7.21 µM) against five human cancer cell lines, including A549, HepG2, HCT116, MDA-MB-231, and CNE2. Compound 6 was further investigated. Compound 6 effectively induced G2/M cell cycle arrest and ROS accumulation in a dose-dependent manner, which further led to apoptosis in cancer cells. Interestingly, compounds 1 and 6 could also activate protective autophagy, which was reported for the first time in sesquiterpene isolated from Carpesium abrotanoides. In addition, compounds 1 and 6 could induce lysosomal biogenesis by 173.2% and 163.7%, respectively. In sum, sesquiterpene lactones from Carpesium abrotanoides could induce apoptosis and protective autophagy in cancer cells, which provide a serial of compounds with potential clinical applications.

Three new carabrane sesquiterpenoid derivatives from the whole plant of Carpesium abrotanoides L.

Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C30 skeleton featuring a methylene-tethered bridge between two sesquiterpene moieties, while dicarabrol C presents the unique linkage of a cyclopentane ring in the molecule. Dicarabrol C exhibited potent inhibitory effects on HL-60 cells with an IC50 value of 3.7 µmol·L-1.

Three new carabrane sesquiterpenoid derivatives from the whole plant of Carpesium abrotanoides L / 中国天然药物

Dicarabrols B and C (1 and 2), two new carabrane sesquiterpenoid dimers, along with one new carabrane sesquiterpenoid (3) were isolated from the whole plant of Carpesium abrotanoides L. Their full structures were established by extensive analysis of HR-ESI-MS and NMR spectroscopic data, and time-dependent density functional theory (TDDFT) electronic circular dichroism (ECD) calculations. Dicarabrol B possesses a novel C

Carpesium abrotanoides (L.) Root as a Potential Source of Natural Anticancer Compounds: Targeting Glucose Metabolism and PKM2/HIF-1α Axis of Breast Cancer Cells.

Carpesium abrotanoides L. (CA) is widely used as a medicinal plant in Asia. The biological activities of the extract from the roots of Carpesium abrotanoides L. (PCA) and its major components were analyzed in this study. PCA was separated and identified with mass spectrometry. Furthermore, we sought to elucidate the anticancer activity of PCA and its mechanisms. PCA exerted its anti-breast cancer activity through inhibiting the expression of glycolysis-related genes, such as glucose transporter 1, lactate dehydrogenase A, and hexokinase 2. Moreover, PCA downregulated the expression of pyruvate kinase M2 and altered its cellular translocation. We also demonstrated PCA is an inhibitor of the PKM2/hypoxia-inducible factor-1α axis, indicating that PCA is potentially useful as an anti-breast cancer agent. PRACTICAL APPLICATION: In this study, the extract from roots of Carpesium abrotanoides Linn. (PCA) was shown to have a noticeable anticancer effect against breast cancer in vitro, and PCA exerts the anticancer activity by regulating glucose metabolism and PKM2 expression. These findings indicate that PCA is a promising agent with practical applications in the development of functional food containing Carpesium abrotanoides L. root extracts.

New eremophilane-type sesquiterpenes and maleimide-bearing compounds from Carpesium abrotanoides L.

Two new eremophilane-type sesquiterpenes, carperemophilanes A and B (1-2), three new maleimide-bearing compounds, carpesiumaleimides A-C (3-5), along with a known sesquiterpene, carabrol (6), were isolated from the ethanol extract of Carpesium abrotanoides L. Their structures were elucidated by analysis of their NMR and MS data as well as by comparison with the literature. The absolute configuration of carperemophilane A (1) was determined by single-crystal X-ray diffraction analysis. All isolated compounds (1-6) were evaluated in vitro for cytotoxicity against two human cancer cell lines MDA-MB-231 and HGC-27 using the MTT method. Compounds 1, 2 and 6 showed cytotoxic activities with IC50 values ranging from 7.45 to 37.35 µM.

Essential Oil from Carpesium abrotanoides L. Induces Apoptosis via Activating Mitochondrial Pathway in Hepatocellular Carcinoma Cells.

The effects of essential oil from Carpesium abrotanoides L. (CAEO) on the proliferation and apoptosis of human hepatic cancer cells were investigated in this study. MTT assays indicated that CAEO inhibited the proliferation of HCC cells with the IC50 values ranging from 41.28±3.06 to 130.36±20.79 µg/mL. Moreover, many obviously nuclear morphological changes of apoptotic cells in CAEO-treated HepG2 cells were detected by Hoechst 33258 staining and fluorescence microscopy. Flow cytometry was used to detect cell apoptosis and cell cycle, and noticeable findings showed that CAEO arrested cell-cycle at S and G2/M phases. The decreased Bcl-2/Bax protein ratio and the activation of caspase-3, caspase-9 were also detected by Western blotting. All results suggested that CAEO is a potential agent to fight against liver cancer, and the mitochondria-mediated intrinsic apoptotic pathway could be involved in CAEO-mediated apoptosis of human liver carcinoma cells.

Caroguaianolide A-E, five new cytotoxic sesquiterpene lactones from Carpesium abrotanoides L.

Five new guaiane-type sesquiterpene lactones, caroguaianolide A-E (1-5), along with nine known sesquiterpene lactones (6-14) were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic date, HRESIMS analysis, and comparison of experimental and calculated ECD data. All isolated compounds (1-14) were tested in vitro for their cytotoxic activities against the MDA-MB-231, HGC-27 cancer cell lines, of which compounds 1-3, 6, 7, 11 and 12 showed significant cytotoxic activities with IC50 values ranging from 2.67 to 12.34 µM.

Terpenes from Carpesium abrotanoides and their cytotoxic activities / 中草药

Objective To study the terpenes from Carpesium abrotanoides and their cytotoxic activities. Methods The separations and purifications were taken by column chromatography over normal phase silica gel, preparative thin-layer chromatography and preparative HPLC. Their chemical structures were elucidated through spectroscopic analyses (NMR). The in vitro cytotoxic activities of the isolated compounds were studied by MTT method. Results Six eudesmane-type sesquiterpenes, one germacrane-type sesquiterpene, one carabrane-type sesquiterpene and one rareseco-sesquiterpenewere obtained and determined as granilin (1), telekin (2), isoalantolactone (3), 3α,5α-dihydroxyisoalantolactone (4), isotelekin (5), asperilin (6), 11(13)-dehydroivaxillin (7), carabrone (8), and Postia secoguaianolide (9), along with two monoterpenes 7,8-epoxy-9-(isobutyryloxy)thymolisobutyrate (10) and 10-hydroxy-8,9-dioxyisopropylidenethymol (11). Conclusion Compounds 9 and 10 are isolated from the genus Carpesium for the first time, compounds 3, 4, 6, and 10 are separated from C. abrotanoides for the first time. And it is the first time to report the 13C-NMR of compounds 4 and 6. Compound 1 shows cytotoxicity against HGC-27 cell and MDA-MB-231 cell with IC50 values of 18.18 μmol/L and 16.17 μmol/L. Compound 2 shows cytotoxicity against HGC-27 cell and MDA-MB-231 cell with IC50 values of 20.65 μmol/L and 17.62 μmol/L. Compound 8 shows cytotoxicity against HGC-27 cell with an IC50 value of 24.96 μmol/L.

Dicarabrol, a new dimeric sesquiterpene from Carpesium abrotanoides L.

A new dimeric sesquiterpene, dicarabrol (1), together with three known sesquiterpenes, carabrol (2), 11(13)-dehydroivaxillin (3), and 2-desoxy-4-epi-pulchellin (4), were isolated from the whole plant of Carpesium abrotanoides L. Their structures were elucidated on the basis of spectroscopic analysis, and single crystal X-ray diffraction analysis. Compound 1 possessed a dimeric sesquiterpene core featured with a cyclopentane ring connecting two sesquiterpene lactone units rarely discovered in nature. Dicarabrol (1), as well as three known sesquiterpenes (2-4), had potent in vitro cytotoxicities against the K562, MCF-7, Hela, DU145, U937, H1975, SGC-7901, A549, MOLT-4, and HL60 cell lines with IC50 values ranging from 0.10 to 46.7 µM, while they showed significant antiviral (H1N1 and H3N2) activities. Furthermore, compounds 1, 3 and 4 displayed significant antimycobacterial activity (IC50 3.7, 6.0, and 7.6 µM, respectively).