RESUMEN
The plants of genus Toona are well known for diverse limonoid secondary metabolites, while polyacetylenes are rarely found from Toona species. In this work, six new polyacetylenes toonasindiynes A-F (1-6) and six known analogues (7-12) were isolated from the root bark of Toona sinensis. Their structures and absolute configurations were elucidated by HRESIMS, 1D and 2D NMR spectroscopic analysis, modified Mosher's method, and biosynthetic consideration. These polyacetylenes share the same 4,6-diyne moiety with different side chain length and different oxidation degree. Bioactivity screening revealed the cytotoxic activity of 3, 5, 9, and 11 against U2OS cells, and the inhibitory effects on nitric oxide (NO) production of 1, 2, 5, 8, 9, and 11 in lipopolysaccharide-induced RAW 264.7 cells.
Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Polímero Poliacetilénico/farmacología , Toona/química , Animales , Antiinflamatorios/aislamiento & purificación , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , China , Humanos , Ratones , Estructura Molecular , Óxido Nítrico/metabolismo , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Raíces de Plantas/química , Polímero Poliacetilénico/aislamiento & purificación , Células RAW 264.7RESUMEN
BACKGROUND: Eucalyptus extracts have anti-cancer activity against various cancer cells. Formyl-phloroglucinol meroterpenoids (FPMs), which are typical secondary metabolites of the genera Eucalyptus, have many important pharmacological activities. PURPOSE: Eucalrobusone C (EC), a new bioactive phytochemical, was first isolated from the leaves of Eucalyptus robusta in our laboratory. EC is a FPM, and our previous research revealed that EC showed strongest cytotoxicity in three cancer models than other compounds isolated from the leaves of E. robusta. This study investigated its anti-tumor effects on human hepatocellular carcinoma (HCC) and its underlying mechanisms. METHODS: Cell viability was measured by MTT assay. Cell cycle, apoptosis and mitochondrial transmembrane potential were determined by flow cytometry. Immunofluorescence was determined by a laser scanning confocal microscope. Protein levels were analyzed by Western blotting. RESULTS: Our results showed that EC exerted strong anti-proliferative activity against HCC cells in a concentration- and time-dependent manner. EC markedly induced apoptosis through the caspase-dependent mitochondrial pathway, and the cell cycle was arrested at S phase. SB203580, a p38 MAPK inhibitor, effectively decreased cell death caused by EC. Moreover, the ROS scavenger N-acetyl cysteine (NAC) significantly attenuated apoptosis induced by EC and reversed EC-induced p38 MAPK activation. CONCLUSION: Our findings indicate that EC induces mitochondrial-dependent apoptosis in HCC cells through ROS generation and p38 MAPK activation, making EC a promising candidate for further development as an anticancer agent for HCC cells.
Asunto(s)
Carcinoma Hepatocelular , Eucalyptus/química , Neoplasias Hepáticas , Mitocondrias/efectos de los fármacos , Extractos Vegetales/farmacología , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patología , Ciclo Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Inhibidores Enzimáticos/farmacología , Células Hep G2 , Humanos , Imidazoles/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Fitoterapia , Extractos Vegetales/uso terapéutico , Piridinas/farmacologíaRESUMEN
Nine formyl-phloroglucinolmeroterpenoids (FPMs), namely, eucalrobusonesâ A-I (1-9), were isolated from the leaves of Eucalyptus robusta by tracking the phenolic hydroxyl (1) Hâ NMR peaks. The Snatzke helicity rules for the Cotton effects of twisted benzene rings were applied to elucidate the absolute configurations of the FPMs. These findings, along with NMR spectroscopy, the circular dichroism (CD) exciton chirality method, and CD calculations, allowed complete structures for the FPMs to be assigned. Eucalrobusonesâ A-F (1-6) are novel adducts formed between a formyl-derived carbon atom on the phloroglucinol ring and monoterpene and sesquiterpene components. Eucalrobusonesâ G-I (7-9) are the first examples of FPMs with cubebane part structures connected by an unusual 1-oxaspiro[5.5]undecane subunit. Among these isolates, eucalrobusoneâ C (3) showed significant cytotoxicity against HepG2, MCF-7, and U2OS cancer cell lines, with IC50 values less than 10â µm. Compound 3 significantly blocks cell proliferation in MCF-7 cells and induces MCF-7 cell death through apoptosis.
Asunto(s)
Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Eucalyptus/química , Floroglucinol/química , Hojas de la Planta/química , Sesquiterpenos/química , Sesquiterpenos/farmacología , Terpenos/química , Terpenos/farmacología , Dicroismo Circular , Humanos , Células MCF-7 , Imagen por Resonancia Magnética , Espectroscopía de Resonancia Magnética , Estructura Molecular , Sesquiterpenos/aislamiento & purificación , Terpenos/aislamiento & purificaciónRESUMEN
Sarglaperoxides A (1) and B (2), a pair of unusual sesquiterpene-normonoterpene conjugates with a peroxide bridge, were isolated from the seeds of Sarcandra glabra. The structures and absolute configurations of 1 and 2 were determined on the basis of spectroscopic data analysis, including MS, NMR, CD, and XRD. The two compounds were screened in antimicrobial, anti-inflammatory, and cytotoxic bioassays and showed moderate bioactivities.