RESUMEN
Novel N-ethy-2-pyrrolidinone-substituted flavonols, myricetin alkaloids A-C (1-3), quercetin alkaloids A-C (4a, 4b, and 5), and kaempferol alkaloids A and B (6 and 7), were prepared from thermal reaction products of myricetin, quercetin, kaempferolâl-theanine, respectively. We used HPLC-ESI-HRMS/MS to detect 1-7 in 14 cultivars of green tea and found that they were all present in "Shuchazao," "Longjing 43", "Fudingdabai", and "Zhongcha 108" green teas. The structures of 1-4 and 6 were determined by extensive 1D and 2D NMR spectroscopies. These flavonol alkaloids along with their skeletal flavonols were assessed for anti-Alzheimer's disease effect based on molecular docking, acetylcholinesterase inhibition, and the transgenic Caenorhabditis elegans CL4176 model. Compound 7 strongly binds to the protein amyloid ß (Aß1-42) through hydrogen bonds (BE: -9.5 kcal/mol, Ki: 114.3 nM). Compound 3 (100 µM) is the strongest one in significantly extending the mean lifespan (13.4 ± 0.5 d, 43.0% promotion), delaying the Aß1-42-induced paralysis (PT50: 40.7 ± 1.9 h, 17.1% promotion), enhancing the locomotion (140.0% promotion at 48 h), and alleviating glutamic acid (Glu)-induced neurotoxicity (153.5% promotion at 48 h) of CL4176 worms (p < 0.0001).
Asunto(s)
Alcaloides , Enfermedad de Alzheimer , Animales , Té/química , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/farmacología , Caenorhabditis elegans/genética , Quercetina/farmacología , Acetilcolinesterasa , Simulación del Acoplamiento Molecular , Alcaloides/farmacología , Alcaloides/química , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/genética , Flavonoles/farmacologíaRESUMEN
Thirteen diterpenoids (1-13), classified into four structurally diverse carbon skeletons, including 1,5-seco-kalmane (1 and 6), grayanane (2-11), kalmane (12), and rhodomollane (13), were isolated from the flowers extract of Rhododendron molle. Among them, rhodomollinols A - E (1-5) were five new diterpenoids and their structures were elucidated by extensive spectroscopic methods including HRESIMS, UV, IR, 1D and 2D NMR, as well as quantum ECD calculations. Rhodomollinol A (1) is the first representative of a 6-deoxy-1,5-seco-kalmane diterpenoid. The abnormal NMR phenomenon of the presence of only 9 carbon resonances instead of 20 carbons in the 13C NMR spectrum of 1 was observed and elucidated by the quantum NMR calculations. All diterpenoids 1-13 showed significant analgesic activities in an acetic acid-induced writhing model. It's the first time to report the analgesic activity of a rhodomollane-type diterpenoid. At a dose of 1.0 mg/kg, diterpenoids 1-3, 6, 8, 9, and 12 reduced the writhe numbers with inhibition rates over 50%, and 9 exhibited stronger analgesic activity with a writhe inhibition rate of 89.7% than that of the positive control morphine. Importantly, even at the lowest dose of 0.04 mg/kg, rhodomollinols A (1) and B (2), rhodomollein X (7), and 2-O-methylrhodojaponin VI (9) still showed more potent analgesic effects than morphine with the writhe inhibition rates of 51.8%, 48.0%, 61.7%, and 60.0%, respectively. A preliminary structure-activity relationship might provide some clues to design potential analgesics on the basis of structurally diverse Ericaceae diterpenoids.
Asunto(s)
Diterpenos , Rhododendron , Rhododendron/química , Estructura Molecular , Flores/química , Analgésicos/farmacología , Diterpenos/farmacología , Diterpenos/química , Carbono/análisis , Derivados de la Morfina/análisisRESUMEN
A systematical investigation on the chemical constituents of the flowers of Rhododendron molle (Ericaceae) led to the isolation and characterization of thirty-eight highly functionalized grayanane diterpenoids (1-38), including twelve novel analogues molleblossomins A-L (1-12). Their structures were elucidated by comprehensive methods, including 1D and 2D NMR analysis, calculated ECD, 13C NMR calculations with DP4+ probability analysis, and single crystal X-ray diffraction. Molleblossomins A (1), B (2), and E (5) are the first representatives of 2ß,3ß:9ß,10ß-diepoxygrayanane, 2,3-epoxygrayan-9(11)-ene, and 5,9-epoxygrayan-1(10),2(3)-diene diterpenoids, respectively. Molleblossomins G (7) and H (8) represent the first examples of 1,3-dioxolane-grayanane conjugates furnished with the acetaldehyde and 4-hydroxylbenzylidene acetal moieties, respectively. All grayanane diterpenoids 1-38 were screened for their analgesic activities in the acetic acid-induced writhing model, and all of them exhibited significant analgesic activities. Diterpenoids 6, 13, 14, 17, 20, and 25 showed more potent analgesic effects than morphine at a lower dose of 0.2 mg/kg, with the inhibition rates of 51.4%, 68.2%, 94.1%, 66.9%, 97.7%, and 60.0%, respectively. More importantly, even at the lowest dose of 0.04 mg/kg, rhodomollein X (14), rhodojaponin VI (20), and rhodojaponin VII (22) still significantly reduced the number of writhes in the acetic acid-induced pain model with the percentages of 61.7%, 85.8%, and 64.6%, respectively. The structure-activity relationship was summarized and might provide some hints to design novel analgesics based on the functionalized grayanane diterpenoids.
Asunto(s)
Diterpenos , Rhododendron , Rhododendron/química , Estructura Molecular , Flores/química , Analgésicos/farmacología , Analgésicos/uso terapéutico , Analgésicos/química , Diterpenos/farmacología , Diterpenos/uso terapéutico , Diterpenos/química , Ácido Acético/análisisRESUMEN
Methylation is a common structural modification of catechins in tea, which can improve the bioavailability of catechins. Flavoalkaloids are catechin derivatives with a nitrogen containing five-membered ring at the C-6 or C-8 position. Here we isolated three new methylated flavoalkaloids from Echa 1 green tea (Camellia sinensis cv. Echa 1) and synthesized another four new methylated flavoalkaloids. The structures of the new ester-type methylated catechins (etmc)-pyrrolidinone A-G (1-7) were elucidated by various spectroscopic techniques, including nuclear magnetic resonance (NMR), optical rotation, infrared, UV-vis, experimental and calculated circular dichroism (CD) spectra, and high-resolution mass. Among them, 6 and 7 showed the strongest α-glucosidase inhibitory activity and significantly lowered lipid content of Caenorhabditis elegans with 73.50 and 67.39% inhibition rate, respectively. Meanwhile, 6 and 7 also exhibited strong antioxidant activity in vitro and stress resistance to heat, oxidative stress, and UV irradiation in nematodes.
Asunto(s)
Camellia sinensis , Catequina , Animales , Té/química , Caenorhabditis elegans , Camellia sinensis/química , AntioxidantesRESUMEN
Green tea polyphenols show positive effects on human health and longevity. However, knowledge of the antiaging properties of green tea is limited to the major catechin epigallocatechin gallate (EGCG). The search for new ingredients in tea with strong antiaging activity deserves further study. Here we isolated and identified two new catechins from Zijuan green tea, named zijuanin E (1) and zijuanin F (2). Their structures were identified by extensive high-resolution mass spectroscopy (HR-MS), nuclear magnetic resonance (NMR), ultraviolet-vis (UV), infrared (IR) and circular dichroism (CD) spectroscopic analyses, and their 13C NMR and CD data were calculated. We used the nematode Caenorhabditis elegans (C. elegans) to analyze the health benefits and longevity effects of 1 and 2. Compounds 1 and 2 (100 µM) remarkably prolonged the lifespan of C. elegans by 67.2% and 56.0%, respectively, delaying the age-related decline of phenotypes, enhancing stress resistance, and reducing ROS and lipid accumulation. Furthermore, 1 and 2 did not affect the lifespan of daf-16, daf-2, sir-2.1, and skn-1 mutant worms, suggesting that they might work via the insulin/IGF and SKN-1/Nrf2 signaling pathways. Meanwhile, 1 and 2 also exhibited strong antioxidant activity in vitro. Surface plasmon resonance (SPR) evidence suggests that zijuanins E and F have strong human serum albumin (HSA) binding ability. Together, zijuanins E and F represent a new valuable class of tea components that promote healthspan and could be developed as potential dietary therapies against aging.
Asunto(s)
Proteínas de Caenorhabditis elegans , Catequina , Animales , Antioxidantes/farmacología , Caenorhabditis elegans , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Catequina/química , Insulina/metabolismo , Lípidos/farmacología , Longevidad , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo , Especies Reactivas de Oxígeno/metabolismo , Albúmina Sérica Humana/metabolismo , Transducción de Señal , Té/químicaRESUMEN
A new megastimane sesquiterpenoid, cassianol A (1), and five known analogues (2-6) were isolated from the leaves extract of Cinnamomum cassia. Their structures were elucidated by extensive spectroscopic methods and single-crystal X-ray diffraction analyses. All the isolates were isolated from C. cassia for the first time. The anti-inflammatory activities of compounds 1-6 were evaluated against nitric oxide (NO) production in LPS-induced RAW 264.7 mouse macrophages.
Asunto(s)
Cinnamomum aromaticum , Sesquiterpenos , Animales , Antiinflamatorios/química , Antiinflamatorios/farmacología , Cinnamomum aromaticum/química , Lipopolisacáridos/farmacología , Ratones , Estructura Molecular , Óxido Nítrico , Extractos Vegetales/química , Sesquiterpenos/farmacologíaRESUMEN
Chronic kidney disease is one of the major worldwide public health problems. Traditional Chinese medications have been widely used for chronic kidney disease treatment. As the development of modern phytochemistry technology, natural products have been isolated from traditional Chinese medications, which provide a more precise method for the investigation of traditional Chinese medications. In this article, we selected eight natural products from traditional Chinese medications for chronic kidney disease therapy to summarize the recent advances for the development of new medications.
Asunto(s)
Productos Biológicos , Medicamentos Herbarios Chinos , Insuficiencia Renal Crónica , Productos Biológicos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Femenino , Humanos , Masculino , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
A total of twenty abietane quinone diterpenoids including ten new ones (1-10) were isolated from the roots extract of Salvia deserta. Their chemical structures were delineated by extensive spectrometric and spectroscopic techniques including HRESIMS, NMR, UV, IR, and single-crystal X-ray diffraction analysis, calculated 13C NMR-DP4+ analysis, calculated ECD, and Mo2(OAc)4-induced ECD. The absolute configurations of salvidesertone A (1), 8α,9α-epoxy-6-deoxycoleon U (18), and 7,20-epoxyroyleanone (19) were determined by single-crystal X-ray diffraction analysis. Salvidesertone A (1) represents the first example of a 9-hydroxyabieta-7(8)-ene quinone diterpenoid. This is the first report of the crystal structures of 8α,9α-epoxy-6-deoxycoleon U (18) and 7,20-epoxyroyleanone (19). Abietane quinone diterpenoids 1, 2, and 4-20 were evaluated for their antiproliferative activities against five cancer cell lines A-549, SMMC-7721, SW480, MCF-7, and HL-60 and a normal epithelial cell line BEAS-2B in vitro. Salvidesertones E (8) and F (9) selectively inhibited the proliferation of A-549, SMMC-7721, and SW480 cancer cell lines. Importantly, salvidesertones E (8) and F (9), horminone (13), taxoquinone (14), 7α-O-methylhorminone (15), and 8α,9α-epoxy-6-deoxycoleon U (18) showed more potent antiproliferative effects against A-549 than the positive control cis-platin. A preliminary structure-activity relationship for the antiproliferative effects of abietane quinone diterpenoids 1-20 was discussed.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Diterpenos/farmacología , Extractos Vegetales/farmacología , Quinonas/farmacología , Salvia/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular , Proliferación Celular/efectos de los fármacos , Cristalografía por Rayos X , Diterpenos/química , Diterpenos/aislamiento & purificación , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Modelos Moleculares , Estructura Molecular , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Raíces de Plantas/química , Quinonas/química , Quinonas/aislamiento & purificación , Relación Estructura-ActividadRESUMEN
Sixteen lanostane-type triterpene glycosides including eight new ones, named lyonicarposides A-H (1-8), were isolated from the flowers of Lyonia ovalifolia var. hebecarpa (Franch. ex F.B. Forbes & Hemsl.) Chun (Ericaceae). The chemical structures of the new compounds were elucidated by the comprehensive spectroscopic techniques and chemical methods. The Mo2(OAc)4-induced electronic circular dichroism method was used to determine the absolute configurations of C-24 in lyonicarposides A (1), C (3), and E (5). This is the first phytochemical study on the flowers of L. ovalifolia var. hebecarpa. All the isolates were evaluated for their antiproliferative activities against SMMC-7721, HL-60, SW480, MCF-7, and A-549 cell lines. Lyonicarposides A (1) and B (2) showed moderate antiproliferative activities against five cancer cell lines with IC50 values ranging from 12.39 to 28.71 µM. Lyonicarposides C (3) and G (7) and lyonifoloside M (12) selectively inhibited the proliferation of HL-60 and MCF-7 cell lines with IC50 values ranging from 13.03 to 17.71 µM. Interestingly, lyonifoloside L (13) selectively inhibited the proliferation of MCF-7 cell line with an IC50 value of 16.27 µM. Their structure-activity-relationships were discussed.
Asunto(s)
Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Ericaceae/química , Triterpenos/química , Triterpenos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Flores/química , Glicósidos/química , Glicósidos/farmacología , Humanos , Neoplasias/tratamiento farmacológico , Relación Estructura-ActividadRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Rhododendron molle G. Don (Ericaceae) (RM) is a natural medicinal plant. Its root extracts have been applied in clinic and proved to be effective in chronic glomerulonephritis and rheumatoid arthritis in China. Surprising, little is understood about the key compound of RM and the exact mechanisms underlying its treatment on kidney diseases. In this study, we will explore whether rhodojaponin II (R-II), as the important compound of RM, also exerts the major effect. MATERIALS AND METHODS: Mouse model of focal segmental glomerulosclerosis was induced by single dose of adriamycin injection. Induced adriamycin nephropathy (ADRN) mice were treated individually with RM root extract (5â¯mg/kg, nâ¯=â¯5), RM root extract (60â¯mg/kg, nâ¯=â¯5), R-II (0.04â¯mg/kg, nâ¯=â¯6) or captopril (30â¯mg/kg, nâ¯=â¯5) for five weeks. Podocyte marker (nephrin and podocin) expressions were examined by immunohistochemical staining and Western Blot analysis. Fibronectin level was evaluated by immunohistochemical staining and Western Blot analysis. Interstitial infiltrated inflammatory cells (CD4+ T cells, CD8+ T cells, and CD68+ macrophages) were examined with immunohistochemical staining. The expressions of NF-ĸB p-p65 and TGF-ß1/Smad pathway associated key proteins, such as TGF-ß1, Smad3, phosphorylated-Smad3 (p-Smad3), and Smad7, were analyzed respectively by Western Blot analysis. RESULTS: RM root extract (5â¯mg/kg) and its important compound R-II (0.04â¯mg/kg) significantly ameliorated proteinuria, podocyte injury, and glomerulosclerosis, meanwhile, they hampered interstitial fibrosis in mice with ADRN. R-II significantly reduced NF-ĸB p65 phosphorylation, interstitial infiltrated CD4+ T cells, CD8+ T cells, and CD68+ macrophages, at the same time, down-regulated TGF-ß1 and p-Smad3 protein expressions in mice with ADRN. CONCLUSION: RM root extract, R-II, could effectively ameliorate proteinuria and kidney injury in ADRN, related to its anti-inflammatory effects, as well as suppression of TGF-ß1/Smad signaling pathway.
Asunto(s)
Antiinflamatorios , Diterpenos , Glomeruloesclerosis Focal y Segmentaria , Extractos Vegetales , Proteinuria , Rhododendron , Proteínas Smad/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Diterpenos/farmacología , Diterpenos/uso terapéutico , Doxorrubicina , Glomeruloesclerosis Focal y Segmentaria/inducido químicamente , Glomeruloesclerosis Focal y Segmentaria/tratamiento farmacológico , Glomeruloesclerosis Focal y Segmentaria/metabolismo , Glomeruloesclerosis Focal y Segmentaria/patología , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Masculino , Ratones Endogámicos BALB C , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Raíces de Plantas , Proteinuria/inducido químicamente , Proteinuria/tratamiento farmacológico , Proteinuria/metabolismo , Proteinuria/patología , Transducción de Señal/efectos de los fármacosRESUMEN
A total of thirteen sesquiterpenoids with diverse skeletons including four new sesquiterpenoids, glandulosines Aâ¯-â¯D (1-4), a new natural product, glandulosine E (5), and eight known sesquiterpene lactones (6-13) were isolated from the roots of Cichorium glandulosum Boiss. et Huet (Asteraceae). Their structures were determined by extensive spectroscopic experiments including NMR, electronic circular dichroism (ECD), calculated ECD, Rh2(OCOCF3)4-induced ECD, and single-crystal X-ray diffraction analysis, as well as chemical methods. This is the first report of the crystal structure of 11ß,13-dihydrolactucin (11). Thirteen isolated sesquiterpenoids (1-13) were evaluated for their anti-inflammatory activities in vitro, and three guaiane sesquiterpene lactones, glandulosine E (5), scorzoside (9), and lactucin (10) showed moderate inhibitory activity against LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages.
Asunto(s)
Antiinflamatorios/farmacología , Asteraceae/química , Raíces de Plantas/química , Sesquiterpenos/farmacología , Animales , Antiinflamatorios/aislamiento & purificación , China , Macrófagos/efectos de los fármacos , Ratones , Estructura Molecular , Fitoquímicos/aislamiento & purificación , Fitoquímicos/farmacología , Células RAW 264.7 , Sesquiterpenos/aislamiento & purificaciónRESUMEN
Nine previously undescribed diterpene glucosides, rhodomicranosides A-I, comprising leucothane, 4,5-seco-ent-kaurane, and grayanane types, respectively, were isolated from the leaves of Rhododendron micranthum, along with seven known diterpenoids. Their structures were elucidated based on extensive spectroscopic analyses such as HRESIMS, 1D and 2D NMR, UV, and IR, and their absolute configurations were determined by various methods including X-ray diffraction analysis, electronic circular dichroism spectroscopy (ECD), calculated ECD, and Mo2(OAc)4-induced ECD, as well as chemical methods. This is the first time to report the crystal structures of leucothane diterpene glycosides. Rhodomicranosides A-C represent the first examples of 15α-hydroxy-leucothane diterpenoids, leucothane diterpene diglucosides, and 9ß-hydroxy-leucothane diterpenoids, respectively. Rhodomicranosides D and E are the second and third examples of 4,5-seco-ent-kaurane diterpenoids, and this is the first time to report 4,5-seco-ent-kaurane-type diterpenoids from the genus of Rhododendron. Rhodomicranosides F and G are the first examples of 5α-H-grayan-1(10),9(11)-diene-6-one diterpenoids. Some isolated diterpenoids were evaluated for their analgesic activity in an acetic acid-induced writhing test, and rhodomicranosides A-E and H, pierisformoside F, iso-grayanotoxin II, and grayanotoxins I, III, and IV showed significant analgesic effects with the percentage inhibitions over 50% at the dose of 1.0â¯mg/kg. In particular, grayanotoxins I and III exhibited more potent analgesic activity than morphine at a dose of 0.2â¯mg/kg, and they showed significant analgesic activity even at a lower dose of 0.04â¯mg/kg with the inhibition rates of 71.5% and 69.3%, respectively. Their preliminary structure-activity relationships were discussed.
Asunto(s)
Analgésicos/química , Analgésicos/farmacología , Diterpenos/química , Rhododendron/química , Analgésicos/administración & dosificación , Animales , China , Cristalografía por Rayos X , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Evaluación Preclínica de Medicamentos/métodos , Femenino , Glucósidos/química , Masculino , Ratones , Estructura Molecular , Hojas de la Planta/química , Plantas Medicinales/químicaRESUMEN
Thirteen new grayanane diterpenoid glucosides, 3- epi-grayanoside B (1), micranthanosides A-E (2-6), 7α-hydroxygrayanoside C (7), micranthanoside F (8), 14ß-acetyoxymicranthanoside F (9), micranthanoside G (10), 14- O-acetylmicranthanoside G (11), 14ß-hydroxypieroside A (12), and micranthanoside H (13), and six known analogues (14-19) were isolated from the leaves of Rhododendron micranthum. The structures of 1-19 were elucidated based on spectroscopic analysis, comparison with literature, and chemical methods. The absolute configurations of 3- epi-grayanoside B (1) and micranthanosides A (2) and C (4) were defined by single-crystal X-ray diffraction analysis. This is the first report of the crystal structures of grayanane diterpenoid glucosides. 3- epi-Grayanoside B (1) represents the first example of a 3α-oxygrayanane diterpenoid glucoside, and micranthanosides A-D (2-5) are the first examples of 5α-hydroxy-1-ß H-grayanane diterpenoids. In addition, micranthanosides C-F (4-6 and 8) and 14ß-acetyoxymicranthanoside F (9) represent the first examples of grayanane glucosides with the glucosylation at C-16. All the grayanane diterpenoid glucosides 1-19 were assayed for their anti-inflammatory, antitumor, and PTP1B inhibitory activities, but did not show significant activities at 40 µM. Grayanane diterpenoid glucosides 1-18 were evaluated for their antinociceptive activity, and compounds 2, 3, 7-10, 12, 13, and 16 showed significant antinociceptive effects with percentage inhibitions in excess of 50%.
Asunto(s)
Diterpenos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Glucósidos/aislamiento & purificación , Rhododendron/química , Analgésicos/aislamiento & purificación , Analgésicos/farmacología , Animales , Antiinflamatorios no Esteroideos/aislamiento & purificación , Antiinflamatorios no Esteroideos/farmacología , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Cristalografía por Rayos X , Diterpenos/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/farmacología , Femenino , Glucósidos/farmacología , Humanos , Masculino , Ratones , Estructura Molecular , Hojas de la Planta/químicaRESUMEN
Thirteen new grayanane diterpenoids (1-13), a new dimeric grayanane diterpenoid, bimollfoliagein A (14), and 15 known analogues (15-29) were isolated from the leaves of Rhododendron molle. The structures of the new compounds (1-14) were determined by extensive spectroscopic data interpretation. The absolute configurations of 1-3, 7, 8, 16, 18, and 24 were defined by single-crystal X-ray diffraction analysis. Mollfoliagein A (1) represents the first example of a 2,3:11,16-diepoxy grayanane diterpenoid, featuring a cis/trans/cis/cis/trans-fused 3/5/7/6/5/5 hexacyclic ring system with a 7,13-dioxahexacyclo[10.3.3.01,11.04,9.06,8.014,17]octadecane scaffold. Diterpenoids 1-29 were evaluated for their anti-inflammatory activities in vitro, and 15, 16, 18, 19, 23-26, 28, and 29 exhibited significant inhibitory activities against nitric oxide production in lipopolysaccharide-induced RAW264.7 mouse macrophages with IC50 values ranging from 2.8 to 35.4 µM. A preliminary structure-activity relationship for the anti-inflammatory activity of diterpenoids 1-29 is discussed.
Asunto(s)
Antiinflamatorios/química , Diterpenos/química , Hojas de la Planta/química , Rhododendron/química , Animales , Antiinflamatorios/farmacología , Línea Celular , Cristalografía por Rayos X/métodos , Diterpenos/farmacología , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Flores/química , Ratones , Resonancia Magnética Nuclear Biomolecular/métodos , Células RAW 264.7RESUMEN
Cassia buds, the immature fruits of Cinnamomum cassia (Lauraceae), are widely consumed as a food spice, dietary supplements, flavoring agents, and preservatives. In this study, cassia buds were phytochemically investigated for the first time, leading to the isolation of 2 new sesquiterpenoids (1 and 2) and 10 known sesquiterpenoids (3-12). Their structures were determined by spectrometric and spectroscopic analyses, including nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and circular dichroism. Cinnamosim A (1) represents the ninth example of the rare cyperane-type sesquiterpenoids. All of the compounds (1-12) isolated from cassia buds were evaluated for antimicrobial activities, with compounds 1-3, 5-8, 11, and 12 exhibiting strong antimicrobial activities against Candida albicans and compounds 6, 7, and 11 showing moderate antibacterial activities against Escherichia coli and Staphylococcus aureus. The present investigation indicated that sesquiterpenoids from cassia buds might be used as potential antimicrobial agents to preserve food.
Asunto(s)
Antiinfecciosos/química , Antiinfecciosos/farmacología , Cinnamomum aromaticum/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Sesquiterpenos/química , Sesquiterpenos/farmacología , Antiinfecciosos/aislamiento & purificación , Candida albicans/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Estructura Molecular , Extractos Vegetales/aislamiento & purificación , Sesquiterpenos/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacosRESUMEN
Six 6,8-di-C-methyl-flavonoids, (2R,3R)-6,8-di-C-methyl-5,7,4'-trihydroxyflavanonol 7-O-ß-d-gluco-pyranoside (1), (2R,3R)-6,8-di-C-methyl-5,7,4'-trihydroxyflavanonol 7-O-ß-d-xylopyranosyl(1â6)-ß-d-glucopyranoside (2), 6,8-di-C-methylkaempferol 7-O-ß-d-glucopyranoside (3), (2R)-farrerol (4a), (2R/2S)-farrerol 7-O-ß-d-glucopyranoside (5), and (2R/2S)-farrerol 7-O-ß-d-xylopyranosyl(1â6)-ß-d-glucopyranoside (6), and four known analogues, farrerol (4b), (2R,3R)-6,8-di-C-methyldihydrokae-mpferol (7), 6,8-di-C-methylkaempferol 7-O-ß-d-glucopyranoside (8), and 6,8-di-C-methylkaempferol (9), were isolated from the twigs and leaves of Rhododendron fortunei. The structures of compounds 1-9 were determined by spectroscopic analyses (HRESIMS, 1D and 2D NMR, and CD) and chemical methods. Compounds 1-9 were evaluated for their neuroprotective effects on the human neuroblastoma SH-SY5Y cells apoptosis induced by hydrogen peroxide (H2O2) and amyloid ß peptide (Aß), respectively. Compounds 1-3 and 5-9 exhibited significant neuroprotective effects against H2O2-induced SH-SY5Y cell apoptosis, and compound 8 exhibited the strongest activity with a improvement of cell viability by about 30% at the concentration of 10µM. Compounds 1-9 showed significant neuroprotective effects against Aß-induced SH-SY5Y cell apoptosis.
Asunto(s)
Flavonoides/química , Fármacos Neuroprotectores/química , Rhododendron/química , Apoptosis , Línea Celular Tumoral/efectos de los fármacos , Flavonoides/aislamiento & purificación , Humanos , Estructura Molecular , Neuroblastoma/patología , Fármacos Neuroprotectores/aislamiento & purificación , Extractos Vegetales/química , Hojas de la Planta/químicaRESUMEN
Sixteen new alkaloids belonging to the galanthamine (1-6), plicamine (7-14), and secoplicamine (15 and 16) classes, together with eight known analogues (17-24), were isolated from Zephyranthes candida. The structures of 1-16 were determined by extensive spectroscopic analyses, and the absolute configurations of 1, 2, 7, 8, and 17 were confirmed by single-crystal X-ray diffraction analysis. The orientation of 3-OCH3 in N-methyl-5,6-dihydroplicane (22) was revised. Alkaloids 3, 12-14, and 18-21 exhibited anti-acetylcholinesterase activities with IC50 values ranging from 0.48 to 168.7 µM. Compounds 10-12, 14, and 16 showed in vitro anti-inflammatory activities with IC50 values ranging from 7.50 to 23.55 µM.
Asunto(s)
Antiinflamatorios no Esteroideos/aislamiento & purificación , Inhibidores de la Colinesterasa/aislamiento & purificación , Inhibidores de la Colinesterasa/farmacología , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Galantamina/aislamiento & purificación , Galantamina/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Liliaceae/química , Plantas Medicinales/química , Acetilcolinesterasa/metabolismo , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/farmacología , Inhibidores de la Colinesterasa/química , Cristalografía por Rayos X , Medicamentos Herbarios Chinos/química , Galantamina/química , Compuestos Heterocíclicos de 4 o más Anillos/química , Concentración 50 Inhibidora , Medicina Tradicional , Conformación Molecular , Estructura Molecular , Resonancia Magnética Nuclear BiomolecularRESUMEN
Six new polycyclic polyprenylated acylphloroglucinols (PPAPs), named hyperisampsins H-M (1-6), were isolated from the aerial parts of Hypericum sampsonii, together with five known analogs (7-11). The structures of 1-6 were established by extensive spectroscopic analyses, including HRESIMS and NMR. In addition, the absolute configurations of these new compounds were determined by electronic circular dichroism (ECD) calculations. Compounds 1 and 2 represent the first examples of PPAPs possessing a unique γ-lactone ring at C-23, while 3-6 differed from normal PPAPs with an unprecedented 1,2-dioxane ring. Compounds 1-7 were evaluated for their cytotoxic activities against a panel of human cancer cell lines in vitro, of which 3, 4, and 6 exhibited significant cytotoxic activities with IC50 values ranging from 0.56 to 3.00 µM. Moreover, compound 3 induces leukemia cell apoptotic death, evidenced by activation of caspase-3, degradation of PARP, up-regulation of Bax, and down-regulation of Bcl-2 and Bcl-xl.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Benzofuranos/farmacología , Hypericum/química , Floroglucinol/química , Quinonas/farmacología , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/metabolismo , Benzofuranos/química , Línea Celular Tumoral , Dicroismo Circular , Ensayos de Selección de Medicamentos Antitumorales , Citometría de Flujo/métodos , Humanos , Concentración 50 Inhibidora , Espectroscopía de Resonancia Magnética , Estructura Molecular , Quinonas/químicaRESUMEN
Three new 1α-alkyldaphnane type diterpenoids, wikstroelides R-T (1-3), together with three known analogs, genkwadane C (4), pimelea factors S6 (5) and S7 (6), two known 1α-alkyldaphnane ketal-lactone type diterpenoids, pimelotides A (7) and C (8), and a known daphnane type diterpenoid, simplexin (9), were isolated from the flower buds of Wikstroemia chamaedaphne. Their structures were elucidated by a combination of spectroscopic analyses including HRESIMS and NMR. Compounds 1-9 were evaluated for their cytotoxic activities in vitro, and most of them exhibited moderate cytotoxic activities with IC50 values ranging from 8.7-22.0 µM.
Asunto(s)
Diterpenos/química , Flores/química , Wikstroemia/química , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Línea Celular Tumoral , Diterpenos/aislamiento & purificación , Humanos , Estructura MolecularRESUMEN
Coumarin derivatives are an important class of C6-C3 plant metabolites that show a variety of bioactivities. Currently, most clinical anticoagulant agents are coumarins, such as warfarin, dicoumarol and acenocoumarol, and patients taking these drugs must be monitored for adverse reactions. In a search for safe and effective anticoagulant compounds from Chinese herbal medicine, a screening procedure on the whole plant of Ainsliaea fragrans was performed. The phytochemical investigation of this plant afforded five new coumarin derivatives, including a pair of natural 4-hydroxycoumarin enantiomers (1), a pair of coumarin enantiomers with a rare polycyclic pyrano[3-2c] carbon skeleton (2) and a 7-hydroxycoumarin derivative (3), together with 5 known biogenetically related compounds (4-8). Enantioseparation of 1 and 2 produced optically pure compounds 1a, 1b, 2a and 2b. The absolute configurations of the new compounds were confirmed by single-crystal X-ray diffraction analysis. In addition, we evaluated the anticoagulant activity of all isolates via activated partial thromboplastin time (APTT), thrombin time (TT) and prothrombin time (PT) assays in vitro and in vivo. Of note, compound 3 displayed potent anticoagulant activity and no significant hepatic or renal toxicity, which could make it a promising agent for further preclinical evaluation for preventing abnormal blood clotting.