RESUMEN
Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2-24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 µM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy.
Asunto(s)
Antiinflamatorios , Ciclooxigenasa 2 , Hypericum , Interleucina-1beta , Interleucina-6 , Macrófagos , Óxido Nítrico , Factor de Necrosis Tumoral alfa , Xantonas , Ratones , Xantonas/farmacología , Xantonas/química , Xantonas/aislamiento & purificación , Animales , Células RAW 264.7 , Óxido Nítrico/metabolismo , Óxido Nítrico/biosíntesis , Antiinflamatorios/farmacología , Antiinflamatorios/química , Ciclooxigenasa 2/metabolismo , Ciclooxigenasa 2/genética , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Interleucina-6/metabolismo , Interleucina-6/genética , Interleucina-6/biosíntesis , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-1beta/genética , Hypericum/química , Lipopolisacáridos/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/químicaRESUMEN
In our research on naturally occurring sesquiterpenes, eight shizukaol-type dimers, one chlorahololide-type dimer, and one sarcanolide-type dimer were isolated from the roots of Chloranthus fortunei. As the project was implemented, we accidentally discovered that shizukaol-type dimers can be converted into peroxidized chlorahololide-type dimers. This potential change was discovered after simulations of the changes in corresponding shizukaols showed that three peroxide products were generated (1-3), indicating that peroxidation reactions occurred. HPLC-HR-MS analysis results obtained for the shizukaol derivatives further demonstrate that the reaction occurred, and the type of substituent of small organic ester moieties at positions C-15' and C-13' of unit B were not decisively related to the reaction. Quantum chemical calculations of the mode dimer further demonstrated this phenomenon. The highest occupied molecular orbital (HOMO)-lowest unoccupied molecular orbital (LUMO) energy of the precursor and production revealed the advantageous yield of 4ß-hydroperoxyl production. Additionally, the potential reaction mechanism was speculated and validated using the free energy in the reaction which successfully explained the feasibility of the reaction. Finally, the anti-inflammatory activity of the precursors and products was evaluated, and the products of peroxidation showed better anti-inflammatory activity.
Asunto(s)
Artefactos , Sesquiterpenos , Antiinflamatorios/farmacología , Sesquiterpenos/químicaRESUMEN
Three novel compounds (1-3) along with twenty-six known compounds, two known steroids (4-5) and twenty-four known phenylpropanoids (6-29) were isolated from the whole plant of Thesium chinense Turcz. The structures of the three new compounds were elucidated on the basis of ESI-MS, HR-ESIMS, 1D and 2D NMR, IR, UV spectroscopic data. The absolute stereochemistry of compound 1 was determined by the Gauge-Including Atomic Orbitals (GIAO) method. The in vitro antioxidant, anti-inflammatory and cytotoxic activities of the isolated compounds were evaluated by DPPH radical-scavenging assay, LPS-activated RAW 264.7 cells model and CCK-8 kit, respectively. Compound 11 showed high antioxidant activity with an SC50 value of 16.2 ± 1.6 µM. Compound 21 showed considerable anti-inflammatory activity with an IC50 value of 28.6 ± 3.0 µM. Compounds 4 and 5 displayed potent cytotoxic activity against human NCI-H292, SiHa, A549, and MKN45 cell lines, with the compound 4 having IC50 values of 17.4 ± 2.4, 22.2 ± 1.1, 9.7 ± 0.9, 9.5 ±0.7 µM, and the compound 5 having all IC50 values less than 0.1 µM in vitro.
Asunto(s)
Antineoplásicos , Antioxidantes , Animales , Ratones , Humanos , Antioxidantes/farmacología , Antioxidantes/química , Línea Celular , Células RAW 264.7 , Antiinflamatorios/farmacología , Antiinflamatorios/química , Estructura MolecularRESUMEN
The present study aimed to identify the composition of the aerial parts of Rubia cordifolia L. A chemical investigation on the EtOAc extracts from the aerial parts of Rubia cordifolia resulted in the isolation of four new anthraquinones, namely Cordifoquinone A-D (1-4), along with 16 known anthraquinones. Their structures were elucidated on the basis of NMR and HR-ESIMS data. All isolates were assessed for their inhibitory effects on NO production in LPS-stimulated RAW 264.7 macrophage cells. Compounds 1, 3 and 10 exhibited significant inhibitory activities with IC50 values of 14.05, 23.48 and 29.23 µmol·L-1, respectively. Their antibacterial activities of four bacteria, Escherichia coli (ATCC 25922), Staphylococcus aureus subsp. aureus (ATCC 29213), Salmonella enterica subsp. enterica (ATCC 14028) and Pseudomonas aeruginosa (ATCC 27853), were also evaluated. Our results indicated that the antibacterial activity of these compounds is inactive.
Asunto(s)
RubiaRESUMEN
Errors in elucidating the structures of four natural classes of prenylated aromatic compounds with 2,3-epoxy, 2,3-dihydroxy, and cyclization with an ortho-phenolic hydroxyl to give a pyran or furan ring moiety are frequent and inevitable. Based on rigorous literature research and a series of chemical transformation experiments, a rule for the rapid determination of these four classes of prenylated derivates based on 13C NMR data was formulated, and 57 corrections featuring these fragments were accordingly reported.
Asunto(s)
Productos Biológicos , Ciclización , Espectroscopía de Resonancia Magnética , Estructura Molecular , FenolesRESUMEN
Twelve hitherto unknown tandem prenylated p-hydroxybenzoic acid derivatives, namely, oberoniamyosurusins A-L, together with five known derivatives, were isolated from an EtOH extract of the whole parts of the plant Oberonia myosurus. Compounds 10, 13, and 17 exhibited moderate inhibitory activity against Staphylococcus aureus subsp. aureus ATCC29213 with MIC50 values ranging from 7.6 to 23 µg/mL. To determine the biosynthetic pathway of this class of tandem prenyl-substituted compounds, the full-length transcriptome of O. myosurus was sequenced, yielding 19.09 Gb of clean data and 10â¯949 nonredundant sequences. Two isoforms of p-hydroxybenzoic acid prenyltransferases were annotated and functionally characterized as the enzymes that might be involved in the biosynthesis of nervogenic acid (13) in Pichia pastoris.
Asunto(s)
Antibacterianos/farmacología , Dimetilaliltranstransferasa/genética , Hidroxibenzoatos/farmacología , Orchidaceae/química , Antibacterianos/aislamiento & purificación , China , Hidroxibenzoatos/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Orchidaceae/enzimología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Prenilación , Staphylococcus/efectos de los fármacosRESUMEN
Six hitherto unknown prenylated 2-phenoxychromones, epimedonin G (1), 7-O-methylepimedonin G (2), and epimedonins H-K (3-6), and two new prenylflavonoids, epimedonin L (7) and 3â³-O-desmethylspinorhamnoside (8), were isolated from an ethanol extract of the aerial parts of Epimedium brevicornum. Their structures were established on the basis of spectroscopic data interpretation. Compound 7 exhibited cytotoxic activity when evaluated against four human cancer cell lines (HL-60, A-549, MCF-7, and SW-480), with IC50 values of <10 µM. In addition, the structures of epimedonins A and B (9a, 10a), recently isolated from E. koreanum, were corrected by reanalysis of the published NMR data.
Asunto(s)
Cromonas/química , Cromonas/farmacología , Epimedium/química , Flavonoides/química , Flavonoides/farmacología , Células A549 , Línea Celular Tumoral , Citotoxinas/química , Citotoxinas/farmacología , Células HL-60 , Humanos , Células MCF-7 , Resonancia Magnética Nuclear Biomolecular/métodos , PrenilaciónRESUMEN
Three hitherto unknown compounds, including one new hispanane-type diterpenoid glucoside, namely viburnumoside (1), two new secoiridoid glucosides, 7α-galloyloxysweroside (2), and 7ß-galloyloxysweroside (3), together with ten known compounds (4 - 13) were isolated from the ethanol extract of twigs and leaves of Viburnum cylindricum. Their structures were elucidated on the basis of extensive spectroscopic studies, and the absolute configuration of compound 1 was confirmed by the experimental and calculated electronic circular dichroism (ECD) data.
Asunto(s)
Diterpenos/química , Glucósidos/química , Glucósidos Iridoides/química , Viburnum/química , Diterpenos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Glucósidos Iridoides/aislamiento & purificación , Estructura Molecular , Teoría CuánticaRESUMEN
Two new prenylflavonoids, morusalbols A and B (1 and 2), were isolated from the branches and leaves of Morus alba, together with three known compounds, kuwanon C (3), morusin (4), morusinol (5). The structures of these two prenylflavonoids were elucidated by extensive analyzes of the spectroscopic data.
Asunto(s)
Flavonoides/aislamiento & purificación , Morus/química , Flavonoides/química , Flavonoides/farmacología , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Hojas de la Planta/químicaRESUMEN
Previous studies on Ranunculus sceleratus L. have shown the existence of coumarins and their anti-inflammatory effect. Phytochemical work was conducted to investigate the bioactive compounds, leading to the isolation of two undescribed benzopyran derivatives, namely ranunsceleroside A (1) and B (3), together with two known coumarins (2, 4) from the whole plant of R. sceleratus L. All compounds were structurally identified by extensive spectroscopic analysis and then investigated for their inhibitory effect on nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6) production induced by lipopolysaccharide (LPS) in RAW 264.7 murine macrophages, repectively. As a result, compound 1-4 presented inhibitory effects on the production of NO, TNF-α, IL-1ß, and IL-6 in a concentration-dependent manner, which provides a potential chemical basis for the traditional use of R. sceleratus L. as an anti-inflammatory plant.
Asunto(s)
Benzopiranos , Ranunculus , Animales , Ratones , Benzopiranos/farmacología , Células RAW 264.7 , Lipopolisacáridos/farmacología , Interleucina-6 , Factor de Necrosis Tumoral alfa , Cumarinas/farmacología , Antiinflamatorios/farmacología , Interleucina-1beta , Óxido NítricoRESUMEN
As our ongoing searching for the bioactive natural terpenoids, nine ent-kauranoids (1-9), including three previously undescribed ones (1, 2, and 9), were isolated from the aerial parts of Isodon amethystoides. Their structures were elucidated on the basis of spectroscopic data analysis, including NMR, MS, and ECD. Compounds 1 and 2 were a pair of tautomeric compounds, which was confirmed by the HPLC analysis and low temperature NMR testing. The underlying mechanism of the tautomer was proposed as an intramolecular SN2 reaction, which was explained by quantum chemical calculation. The HOMO-LUMO gap and the free energy revealed the spontaneous of the tautomeric of the 1 and 2. Additionally, the similar phenomena were also found in the two groups of known compounds 3 and 4 and 6 and 7, respectively. Apart from the tautomer, compounds 3 and 4 can be hydrolyzed into 5 through ester hydrolysis in CDCl3, while compounds 6, 7 can be hydrolyzed into 8 through ester hydrolysis. These phenomena were also confirmed through HPLC analysis and low temperature nuclear magnetic resonance tests and the mechanism was studied using quantum chemical calculation.
Asunto(s)
Antineoplásicos Fitogénicos , Diterpenos de Tipo Kaurano , Isodon , Estructura Molecular , Isodon/química , Componentes Aéreos de las Plantas/química , Ésteres , Ensayos de Selección de Medicamentos AntitumoralesRESUMEN
Actinomadura sp., which is usually found in muddy habitats, produces various secondary metabolites with biological activities. In this study, five new compounds named formosensin A (1), formosensin B (2), oxanthroquinone-3-O-α-d-mannose (8), oxanthromicin A (9), and oxanthromicin B (10) were isolated from the culture of Actinomadura sp. together with five known compounds (3-7). Their structures were elucidated by extensive spectroscopic methods including NMR and MS. In particular, the absolute configurations of compounds 1 and 2 were determined using computational methods. Moreover, compounds 1-2 and 8-10 were screened for cytotoxic activity using a panel of human tumor cell lines. Compound 9 induced significant cytotoxicity in five human tumor cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480) with IC50 values of 8.7, 17.5, 15.0, 17.8, and 14.6 µM, respectively. These findings suggested that compound 9 could provide therapeutic benefits in the treatment of tumor-related diseases.
Asunto(s)
Actinomadura , Antineoplásicos , Humanos , Estructura Molecular , Antineoplásicos/farmacología , Línea Celular Tumoral , AntraquinonasRESUMEN
Eleven previously unreported compounds (1-11), including five diterpenoids (1-5) and six sesquiterpenoids (6-11), together with two known diterpenoids (12-13), have been isolated from the roots of Salvia prattii. Their structures were comprehensively elucidated through spectroscopic methods, and their configurations were established using computational 13C nuclear magnetic resonance and electronic circular dichroism. Compound 1 was found to be an abietane-type diterpenoid with a novel rearrangement generated from the cleavage of the C-4/5 chemical bond, 20-methyl shift, and the rearrangement of the C-10 side chain. Compounds 2-3 were the third and fourth examples of arrangement seco-norabietanes with a spiro-lactone ring. We evaluated all compounds for their protective effects against alcoholic liver diseases (ALD). Compound 2 exhibited potential protective activity and hence can be used as a novel anti-ALD candidate.
Asunto(s)
Diterpenos , Salvia , Terpenos/farmacología , Estructura Molecular , Salvia/química , Diterpenos/farmacología , Diterpenos/química , Abietanos/farmacología , Abietanos/químicaRESUMEN
Six new ent-15-oxokauran-19-oic acid derivatives, named pterisolic acids A-F (1-6), were isolated from the ethanol extract of the fern Pteris semipinnata (Pteridaceae), and the structures of these new ent-kauranoids were elucidated on the basis of extensive spectroscopic studies and single crystal X-ray diffraction analysis.
Asunto(s)
Diterpenos de Tipo Kaurano/química , Pteris/química , Cristalografía por Rayos X , Conformación MolecularRESUMEN
Four new neo-clerodane diterpenoids, scutebarbatines W-Z (1-4), were isolated from the ethanol extract of Scutellaria barbata (Labiatae), and their structures were elucidated on the basis of extensive spectroscopic studies. In addition, the proposed structures of at least seven 13-spiro subtype neo-clerodanes: scutehenanine B (5), scutebarbatine G (6), 6-O-nicotinoylscutebarbatine G (7), barbatin A (8), 6,7-di-O-nicotinoylscutebarbatine G (9), 6-O-nicotinoyl-7-O-acetylscutebarbatine G (10), and scutebarbatine F (11), reported by Dai and co-workers from the same species, were incorrectly assigned and have been revised by reanalysis of the published NMR data.
Asunto(s)
Diterpenos de Tipo Clerodano/química , Extractos Vegetales/química , Scutellaria/química , Diterpenos de Tipo Clerodano/aislamiento & purificación , Espectroscopía de Resonancia Magnética , Estructura Molecular , Extractos Vegetales/aislamiento & purificaciónRESUMEN
The first total synthesis of gastrodinol, an unprecedented poly-p-cresol-substituted natural product with a rearranged and reconstructed C ring moiety, is reported. Our synthesis features a convergent fragment approach. The Sonogashira coupling reaction forges the two segments together to furnish the conjugated ene-yne. Photocatalytic 6π electrocyclization followed by spontaneous aromatization is used to construct the tetrasubstituted B ring at the late stage. Further study shows that gastrodinol exhibits significant cytotoxic activity against five human cancer cell lines in vitro (IC50 2.5-3.8 µM).
RESUMEN
α-mangostin, a polyphenol xanthone derivative, was mainly isolated from pericarps of the mangosteen fruit (Garcinia mangostana L.). In present investigation, a series of derivatives were designed, synthesised and evaluated in vitro for their inhibitory activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Among the synthesised xanthones, compounds 1, 9, 13 and 16 showed AChE selective inhibitory activity, 15 was a BuChE selective inhibitor while 2, 3, 5, 6, 7, 12 and 14 were dual inhibitors. The most potent inhibitor of AChE was 16 while 5 was the most potent inhibitor of BuChE with IC50 values of 5.26 µM and 7.55 µM respectively.
Asunto(s)
Inhibidores de la Colinesterasa/química , Garcinia mangostana/química , Xantonas/síntesis química , Acetilcolinesterasa/efectos de los fármacos , Butirilcolinesterasa/efectos de los fármacos , Inhibidores de la Colinesterasa/farmacología , Diseño de Fármacos , Frutas/química , Xantonas/química , Xantonas/farmacologíaRESUMEN
Two polysaccharides, named DOP-1 and DOP-2, with molecular weights of 6.8 kDa and 14.3 kDa, respectively, were isolated and purified from the stems of Dendrobium officinale. Monosaccharide composition, Fourier-transform infrared spectroscopy, methylation, and nuclear magnetic resonance analyses indicated that DOP-1 and DOP-2 may have a backbone consisted of â4)-ß-d-Glcp-(1â, â4)-ß-d-Manp-(1â, â4)-2-O-acetyl-ß-d-Manp-(1â and â4)-3-O-acetyl-ß-d-Manp-(1â. In vivo assays showed that D. officinale polysaccharides (DOPs) exerted significant hypoglycemic effects accompanying increased serum insulin and glucagon-like peptide-1 (GLP-1) levels in streptozotocin-induced diabetic rats. Further in vitro experiments showed that DOP-induced GLP-1 secretion was inhibited by an intracellular calcium chelator, a Ca2+/calmodulin-dependent protein kinase (CaMK) II inhibitor, a specific calcium-sensing receptor antagonist, and a p38-mitogen-activated protein kinases (MAPK) inhibitor. These results indicated that DOPs may decrease fasting blood sugar levels by stimulating GLP-1 secretion and that intracellular DOP-induced GLP-1 secretion involved the Ca2+/calmodulin/CaMKII and MAPK pathways.
Asunto(s)
Dendrobium/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Péptido 1 Similar al Glucagón , Hipoglucemiantes , Extractos Vegetales , Polisacáridos , Animales , Línea Celular , Péptido 1 Similar al Glucagón/sangre , Péptido 1 Similar al Glucagón/metabolismo , Hipoglucemiantes/química , Hipoglucemiantes/farmacología , Secreción de Insulina , Masculino , Ratones , Extractos Vegetales/química , Extractos Vegetales/farmacología , Polisacáridos/química , Polisacáridos/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
One hitherto unknown 24-nor-13,27-cycloursane-type triterpenoid, lucumic acid A (1), one new 24-nor-ursane triterpenoid, lucumic acid B (2), along with six known triterpenoids were isolated from the ethanol extract of the leaves of Lucuma nervosa. Their structures were established on the basis of spectroscopic data interpretation. Lucumic acid A (1) is the first example of a 24-nor-triterpenoid with a 13,27-cyclopropane ring.
Asunto(s)
Ácido Oleanólico/análogos & derivados , Hojas de la Planta/química , Pouteria/química , Triterpenos/aislamiento & purificación , China , Inhibidores de Glicósido Hidrolasas/aislamiento & purificación , Inhibidores de Glicósido Hidrolasas/farmacología , Estructura Molecular , Ácido Oleanólico/aislamiento & purificación , Ácido Oleanólico/farmacología , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Extractos Vegetales/química , Triterpenos/farmacologíaRESUMEN
Ten previously undescribed stilbenoids, including six bibenzyls (bleochrins A-F, 1-6), three phenanthrenes derivatives (bleochrins G-J, 7-10) along with eleven known compounds were isolated from the rhizomes of Bletilla ochracea Schltr. The structural characterizations of 1-21 were accomplished by spectroscopic data, while the absolute stereostructure of 6 was confirmed by electronic circular dichroism (ECD) data analyses. All isolated metabolites except 7 were evaluated for cytotoxic activity against five human cancer cell lines (HL-60, SMMC-7721, A-549, MCF-7 and SW480). Four isolates exhibited significant inhibitory ability against HL-60, SMMC-7721, and MCF-7 cell lines, with IC50 values ranging from 0.79 to 6.57⯵M. The isolates were tested further for inhibitory effects on the NO production of the liposaccharide (LPS)-induced RAW264.7 macrophages and showed activity with IC50 values at 15.29-24.02⯵M.