RESUMEN
One new canthinone glycoside (1), together with six known compounds (2-7) including three lignans (2-4), two coumarins (5-6) and one phenol (7) was isolated from the root barks of Ailanthus altissima. The structure of new compound 1 was established by the interpretation of UV, IR, MS and NMR data, while its absolute configuration was determined by acid hydrolysis and GIAO NMR calculations with DP4+ probability analysis. The inhibitory effects of all compounds on Nitric oxide (NO) production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 2 and 5 displayed NO production inhibitory activity with IC50 values of 30.1 and 15.3 µM, respectively.
Asunto(s)
Ailanthus , Glicósidos , Lipopolisacáridos , Óxido Nítrico , Corteza de la Planta , Raíces de Plantas , Ailanthus/química , Óxido Nítrico/antagonistas & inhibidores , Óxido Nítrico/biosíntesis , Ratones , Estructura Molecular , Animales , Corteza de la Planta/química , Raíces de Plantas/química , Células RAW 264.7 , Glicósidos/farmacología , Glicósidos/química , Glicósidos/aislamiento & purificación , Lipopolisacáridos/farmacología , Lignanos/farmacología , Lignanos/química , Lignanos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Cumarinas/farmacología , Cumarinas/química , Cumarinas/aislamiento & purificación , Resonancia Magnética Nuclear BiomolecularRESUMEN
Two new guaianolide-type sesquiterpenoids chrysanthemulides K and L (1 and 2), together with six known analogues (3-8), were isolated from an CH2Cl2 extract of the aerial parts of Chrysanthemum indicum. The structures of new compounds 1 and 2 were established by extensive spectroscopic analysis, including UV, IR, MS, NMR and computational electronic circular dichroism (ECD) methods. Inhibitory effects of all compounds on nitric oxide production were investigated in lipopolysaccharide (LPS)-induced RAW 264.7 cells. Results showed that compounds 1-8 displayed NO production inhibitory activity with IC50 values ranged from 3.5 to 34.3 µM.
Asunto(s)
Chrysanthemum , Sesquiterpenos , Animales , Ratones , Chrysanthemum/química , Células RAW 264.7 , Sesquiterpenos/química , Extractos Vegetales/farmacología , Espectroscopía de Resonancia Magnética , Óxido Nítrico , Estructura Molecular , Lipopolisacáridos/farmacologíaRESUMEN
One new 6a,11a-dehydropterocarpan derivative, 6-O-methyl-anhydrotuberosin (1), one new 6a-hydroxypterocarpan, (6aR,11aR,11bR)-hydroxytuberosone (7), and seven known compounds including two 6a,11a-dehydropterocarpans (2 and 4), two coumestans (3 and 5), one isoflavonoid (6) and two other phenolic compounds (8 and 9) were isolated from the roots of Pueraria lobata. The structures of the isolated compounds were elucidated with spectroscopic and spectrometric methods (1 D and 2DNMR, HRESIMS). Compounds 1, 2, 4-5 showed potent LSD1 inhibitory activities with IC50 values ranging from 1.73 to 4.99 µM. Furthermore, compound 2 showed potent cytotoxicity against gastric cancer cell lines MGC-803 and BGC-823, and lung cancer cell lines H1299 and H460.
Asunto(s)
Isoflavonas , Pueraria , Pueraria/química , Línea Celular , Fenoles , Histona Demetilasas/análisis , Raíces de Plantas/química , Isoflavonas/farmacología , Isoflavonas/químicaRESUMEN
Penispidins A-C (1-3), new aromatic sesquiterpenoids with two classes of rare carbon skeletons, were isolated from the endophytic fungus Penicillium virgatum HL-110. 1 represents the first example of a dunniane-type aromatic sesquiterpenoid, possessing a novel 4/6/6 tricyclic system, while (±)-2 and 3 have a 7,12-cyclized bisabolene skeleton, featuring a 3,4-benzo-fused 2-oxabicyclo[3.3.1]nonane central framework. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and ECD calculations. 1 inhibited hepatic lipid accumulation in HepG2 cells.
Asunto(s)
Metabolismo de los Lípidos/efectos de los fármacos , Penicillium/química , Sesquiterpenos/farmacología , China , Células Hep G2 , Humanos , Estructura Molecular , Sesquiterpenos/aislamiento & purificación , Triglicéridos/metabolismoRESUMEN
ABSTACTA chemical investigation of the whole plant of traditional Chinese medicine, Chrysanthemum indicum L., led to the discovery of six guaianolide-type sesquiterpenoids 1-6 with a 1,10-splited skeleton. The structure of the new compound 1 was established by extensive analysis of UV, IR, MS, NMR and ECD data. Compounds 3-6 are mutually stereoisomers with four chiral centers and their absolute configurations were determined by comparison of ECD spectra. The anti-inflammatory effects of these isolates on lipopolysaccharide (LPS)-induced nitric oxide (NO) were investigated in RAW 264.7 cells. Results showed that most of the compounds displayed NO production inhibitory activities with IC50 values ranged from 3.54 to 8.17 µM.
Asunto(s)
Chrysanthemum , Sesquiterpenos , Animales , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico , Células RAW 264.7 , Sesquiterpenos/farmacologíaRESUMEN
Osteosarcoma is the most frequent malignant primary bone tumor, and it generally develops a multidrug resistance. Chrysanthemulide A (CA) is a sesquiterpenoid from the herb Chrysanthemum indicum that has demonstrated a great anti-osteosarcoma potential. In this study, CA-induced apoptotic cell death resulted in the activation of the caspase-8-mediated caspase cascade, as evidenced by the cleavage of the substrate protein Bid and the caspase-8 inhibitor Z-VAD-FMK. The CA treatment upregulated the expression of death receptor 5 (DR5) in both whole cells and the cell membrane. Blocking DR5 expression by the small interfering RNA (siRNA) treatment decreased the caspase-8-mediated caspase cascade and efficiently attenuated CA-induced apoptosis, suggesting the critical role of DR5 in CA-induced apoptotic cell death. CA-induced upregulation of the DR5 protein was accompanied by the accumulation of LC3B-II, indicating the formation of autophagosomes. Importantly, DR5 upregulation was mediated by transcriptionally controlled autophagosome accumulation, as blockade of autophagosomes by LC3B or ATG-5 siRNA substantially decreased DR5 upregulation. Furthermore, CA activated the c-Jun N-terminal kinase (JNK) signaling pathway, and treatment with JNK siRNAs or inhibitor SP600125 significantly attenuated CA-mediated autophagosome accumulation and DR5-mediated cell apoptosis. Finally, CA sensitized the osteosarcoma cells to the DR5 ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptotic cell death. Above all, these results suggest that CA induces apoptosis through upregulating DR5 via JNK-mediated autophagosome accumulation and that combined treatment with CA and TRAIL might be a promising therapy for osteosarcoma.
Asunto(s)
Antineoplásicos/farmacología , Autofagosomas/efectos de los fármacos , Neoplasias Óseas/patología , Osteosarcoma/patología , Extractos Vegetales/farmacología , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Apoptosis/efectos de los fármacos , Autofagosomas/metabolismo , Neoplasias Óseas/metabolismo , Línea Celular Tumoral , Chrysanthemum , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Osteosarcoma/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/efectos de los fármacos , Sesquiterpenos/farmacología , Regulación hacia ArribaRESUMEN
A synthesis-inspired chemical investigation of the leaves of Melicope ptelefolia led to the isolation of evodialones A-D (1-4), four rearranged acetophenone stereoisomers possessing a prenylated acylcyclopentenone skeleton with three stereogenic carbons. Evodialones C and D (3 and 4) are new minor constituents. The chiral-phase HPLC resolution gave (+)-1-4 and (-)-1-4, eight enantiomers forming a complete stereoisomer library. Their absolute configurations were elucidated via extensive spectroscopic data and a modified Mosher's method. The relationship between the chiral structures and their NMR and ECD data is discussed. Compounds (±)-1, -2, and -4 have significant protective effects on high-glucose-induced oxidative stress in human vein endothelial cells.
Asunto(s)
Acetofenonas/química , Células Endoteliales/química , Hojas de la Planta/química , Rutaceae/química , Cromatografía Líquida de Alta Presión , Humanos , Espectroscopía de Resonancia Magnética , Prenilación , EstereoisomerismoRESUMEN
Artemisianins A-D (1-4), four stereoisomers of sesquiterpenoid dimers, forming via [4+2] cycloaddition from a 1, 10-seco-guaianolide dienophile and a guaianolide diene, along with two biosynthetically related precurors 5 and 6, were isolated from the famous traditional Chinese medicine Artemisia argyi. The structures of 1-4, including their absolute configurations, were elucidated by extensive spectroscopic data and ECD/TDDFT calculation analysis. Compounds 1-4 exhibited cytotoxicity with IC50 values ranging from 7.2 to 23.3⯵M. The accumulation of Ca2+ in cytoplasm and enlarged endoplasmic reticulum (ER) indicated that 1 mediated HT-29 cancer cell apoptosis through improvement of ER-stress, which was further proved by unfolded protein response (UPR) pathway on basis of the upregulation of IRE1α, p-PERK, ATF6, and CHOP.
Asunto(s)
Apoptosis , Artemisia/química , Estrés del Retículo Endoplásmico , Sesquiterpenos/química , Apoptosis/efectos de los fármacos , Artemisia/metabolismo , Línea Celular Tumoral , Dimerización , Estrés del Retículo Endoplásmico/efectos de los fármacos , Humanos , Medicina Tradicional China , Conformación Molecular , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Sesquiterpenos/aislamiento & purificación , Sesquiterpenos/farmacología , EstereoisomerismoRESUMEN
Ten new highly oxidized monomeric (1-8) and dimeric guaianolides (9 and 10), along with two known guaianolide derivatives (11 and 12), were isolated from the aerial parts of Chrysanthemum indicum using a bioassay-guided fractionation procedure. The new compounds were characterized by the basic analysis of the spectroscopic data obtained, and the absolute configurations were determined by both empirical approaches and ECD calculations. Inhibitory effects of 1-12 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and most of them (1-8 and 11) displayed IC50 values in the range 1.4-9.7 µM. Moreover, a mechanistic study revealed that the potential anti-inflammatory activity of compound 1 appears to be mediated via suppression of an LPS-induced NF-κB pathway and down-regulation of MAPK activation.
Asunto(s)
Antiinflamatorios/química , Chrysanthemum/química , Sesquiterpenos de Guayano/química , Sesquiterpenos de Guayano/farmacología , Animales , Antiinflamatorios/farmacología , Línea Celular , Lipopolisacáridos/farmacología , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Extractos Vegetales/química , Extractos Vegetales/farmacología , Células RAW 264.7RESUMEN
A total of nine new phenolic amides (1-9), including four pairs of enantiomeric mixtures (3-5 and 8), along with ten known analogues (10-19) were identified from the fruits of Lycium barbarum using bioassay-guided chromatographic fractionation. Their structures were elucidated by comprehensive spectroscopic and spectrometric analyses, chiral HPLC analyses, and quantum NMR, and electronic circular dichroism calculations. Compounds 5-7 are the first example of feruloyl tyramine dimers fused through a cyclobutane ring. The activity results indicated that compounds 1, 11, and 13-17 exhibited remarkable inhibition against α-glucosidase with IC50 of 1.11-33.53 µM, 5-150 times stronger than acarbose (IC50 = 169.78 µM). Meanwhile, compounds 4a, 4b, 5a, 5b, 13, and 14 exerted moderate agonistic activities for peroxisome proliferator-activated receptor (PPAR-γ), with EC50 values of 10.09-44.26 µM. Especially,compound 14 also presented inhibitory activity on dipeptidyl peptidase-4 (DPPIV), with an IC50 value of 47.13 µM. Furthermore, the banding manner of compounds 14 and 17 with the active site of α-glucosidase, DPPIV, and PPAR-γ was explored by employing molecular docking analysis.
Asunto(s)
Lycium , alfa-Glucosidasas , alfa-Glucosidasas/análisis , Frutas/química , Lycium/química , Receptores Activados del Proliferador del Peroxisoma , Agonistas de PPAR-gamma , Amidas , Simulación del Acoplamiento Molecular , Fenoles/análisis , Espectroscopía de Resonancia Magnética , Dipeptidil-Peptidasas y Tripeptidil-Peptidasas/análisis , Estructura Molecular , Inhibidores de Glicósido Hidrolasas/farmacología , Inhibidores de Glicósido Hidrolasas/químicaRESUMEN
Six new flavonols, including four glucosylated flavonols (dysosmaflavonoid A-D), one phenylpropanoid-substituted flavonol (dysosmaflavonoid E), and one phenyl-substituted flavonol (dysosmaflavonoid F), together with five known analogues, were isolated from the roots and rhizomes of Dysosma versipellis. Their structures were elucidated by comprehensive analysis of their NMR, IR, UV, HRESIMS, and HPLC data. The antioxidant activities of all isolated compounds were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Compounds 2, 3, 5-8, and 12 exhibited significant DPPH scavenging capacity with IC50 values of 33.95, 39.02, 31.17, 32.79, 31.85, 30.48, and 23.75 µM, respectively, in comparison with Trolox (IC50, 15.80 µM). Compound 12 displayed more potent DPPH radical scavenging activity than prenylated and (or) glucosided derivatives (2-4, or 10). The preliminary structure-activity relationship showed that the catechol structure in flavonol is essential for DPPH radical scavenging effect.
Asunto(s)
Berberidaceae , Flavonoles , Flavonoles/farmacología , Flavonoles/química , Estructura Molecular , Antioxidantes/farmacología , Antioxidantes/química , Berberidaceae/química , Relación Estructura-Actividad , Depuradores de Radicales Libres/química , Compuestos de Bifenilo , Picratos/químicaRESUMEN
Three new monomeric (1-3) and two newdimeric guaianolides (4 and 5), along with three known analogues (6-8) were isolated from the aerial part of Achillea alpina L. Compounds 1-3 were three novel 1,10-seco-guaianolides, while 4 and 5 were two novel 1,10-seco-guaianolides involved heterodimeric [4 + 2] adducts. The new structures were elucidated by analysis of spectroscopic data and quantum chemical calculations. All isolates were evaluated for their hypoglycemic activity with a glucose consumption model in palmitic acid (PA)-induced HepG2-insulin resistance (IR) cells, and compound 1 showed the most promising activity. A mechanistic study revealed that compound 1 appeared to mediate hypoglycemic activity via inhibition of the ROS/TXNIP/NLRP3/caspase-1 pathway.
Asunto(s)
Achillea , Sesquiterpenos , Achillea/química , Estructura Molecular , Hipoglucemiantes/farmacología , Extractos Vegetales/química , Sesquiterpenos/farmacología , Sesquiterpenos/químicaRESUMEN
Investigation into the chemical diversity of Nardostachys chinensis Batal led to the discovery of three new (1-3) and one known (4) iridoid glycosides. Their structures were established through spectroscopic methods including 1 D and 2 D NMR experiments and HRESIMS analysis. Inhibitory effects of 1-4 on nitric oxide production were investigated in lipopolysaccaride (LPS)-mediated RAW 264.7 cells, and they displayed IC50 values in the range 7.8-15.2 µM.
Asunto(s)
Nardostachys , Animales , Glicósidos/farmacología , Glicósidos Iridoides/farmacología , Espectroscopía de Resonancia Magnética , Ratones , Nardostachys/química , Óxido Nítrico , Células RAW 264.7RESUMEN
Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A-H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1ß,2ß:4ß,5ß-diepoxy-10ß-hydroxy-6ßH,7αH,11ßH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D-F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56-6.25 µM. Moreover, achigermalide D decreased the expression of IL-1ß and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.
Asunto(s)
Achillea , Resistencia a la Insulina , Sesquiterpenos , Achillea/metabolismo , Glucosa , Células Hep G2 , Humanos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ácido Palmítico/farmacología , Especies Reactivas de Oxígeno/metabolismo , Sesquiterpenos/química , Sesquiterpenos/farmacología , Sesquiterpenos de GermacranoRESUMEN
(±)-Hypeisoxazole A (1), a racemic pair of rearranged benzylisoquinoline alkaloids possessing an unprecedented diindeno[2,1-c:2',1'-d] isoxazole scaffold, was isolated from the medicinal herb Hypecoum erectum, along with hypecoleptopine (2), whose structure is now revised as a novel spiro-benzylisoquinoline alkaloid with a 6/6/5/6/6 skeleton. Their structures were determined by comprehensive spectroscopic and spectrometric analyses, X-ray diffraction, and computational studies. Racemic mixture of 2 and its pure enantiomers modulated neuronal excitability activity.
Asunto(s)
BencilisoquinolinasRESUMEN
Ochracines F-L (1-7), seven previously undescribed chamigrane and cadinane sesquiterpenoids, together with four known chamigranes were isolated from cultures of the wood-decaying fungus Steccherinum ochraceum HFG119. Ochracines F-L were structurally characterized by extensive analysis of HRMS and NMR spectroscopic data. The relative configurations were assigned through a combination of NOE correlations and J-based configuration analysis (JBCA), while the absolute configurations were determined by X-ray single-crystal diffraction, and calculated methods (ECD, [α], 13C NMR). All the new isolates were evaluated for their cytotoxicity against five human cancer cell lines HL-60, SMMC-7721, A549, MCF-7, and SW-480, and inhibitory activity on NO production in RAW 264.7 macrophages.
RESUMEN
Two new monoterpene indole alkaloid glycosides nutanoside A-B (1-2), two new phenolic glycoside esters nutanester A-B (6-7), together with five known compounds (3-5, 8-9) were isolated from the ethanol extract of Gardneria nutans Siebold & Zuccarini. Their structures were established on the basis of extensive spectroscopic analysis and TDDFT/ECD calculations. Compounds 1 and 2 are two rare monoterpene indole alkaloids with the glucosyl moiety located at C-12 and represent the first two examples of enantiomer of ajmaline type monoterpene indole alkaloids. Compounds 3, 4 and 6 displayed significant inhibitory effects on NO production in over-activated BV2 microglial cells, with the IC50 values of 2.29, 6.36, and 8.78 µM, respectively. Compounds 1, 5, 7 could significantly inhibit the mRNA expression of inflammatory factors TNF-α and IL-6 induced by LPS in BV2 microglial cells at the effective concentration. Moreover, compound 3 exhibited stronger cytotoxicities against U87 and HCT116 cell lines than taxol with IC50 values of 10.58 and 14.60 µM, respectively.
RESUMEN
[This corrects the article DOI: 10.1039/D1RA05204G.].
RESUMEN
Three tetrahydroquinoline alkaloids, lycibarbarines A-C (1-3), possessing a unique tetracyclic tetrahydroquinoline-oxazine-ketohexoside fused motif, were isolated from the fruits of Lycium barbarum. Their structures were determined by spectroscopic analysis and quantum-chemical calculations. Compounds 1 and 3 exhibited neuroprotective activity when evaluated for corticosterone-induced injury by reducing the apoptosis of PC12 cells through the inhibition of caspase-3 and caspase-9.
Asunto(s)
Alcaloides/química , Caspasa 3/química , Medicamentos Herbarios Chinos/farmacología , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/química , Quinolinas/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Frutas/química , Lycium/química , Lycium/efectos de los fármacos , Estructura Molecular , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/aislamiento & purificación , Células PC12 , Quinolinas/química , Quinolinas/aislamiento & purificación , RatasRESUMEN
Two new flavonoid glucosides, sinoflavonoidgs A (1) and B (2), along with three known analogues 3-5, were isolated from the fruits of Sinopodophyllum hexandrum. Their structures were established on the basis of extensive spectroscopic (UV, IR, HR-ESI-MS, 1H-NMR, 13C-NMR, HSQC, HMBC) and chromatographic (HPLC) analysis. The isolation of compounds 1-2 represents the first report of ring B-glucosided flavonoids from the genus Sinopodophyllum. The cytotoxic activities of all isolated compounds were evaluated in comparison with etoposide against four cell lines (MCF-7, HepG2, HeLa, KB). The antioxidant activities of all isolated compounds were examined by DPPH free radical-scavenging assay. The preliminary structure-activity relationships showed that the glycosilation of 3-methoxyquercetin at C-3' resulted in a greater decrease of cytotoxic and antioxidant activity.