RESUMEN
A series of chalcones containing naphthalene moiety 4a-4p have been synthesized, characterized by 1H NMR and 13C NMR and evaluated for their in vitro anticancer activity. The majority of the screened compounds displayed potent anticancer activity against both HCT116 and HepG2 human cancer cell lines. Among the series, compound 4h with a diethylamino group at the para position of the phenyl ring exhibited the most potent anticancer activity against HCT116 and HepG2 cell lines with IC50 values of 1.20⯱â¯0.07 and 1.02⯱â¯0.04⯵M, respectively. The preliminary structure-activity relationship has been summarized. Tubulin polymerization experiments indicated that 4h effectively inhibited tubulin polymerization and flow cytometric assay revealed that 4h arrests HepG2 cells at the G2/M phase in a dose-dependent manner. Furthermore, molecular docking studies suggested that 4h binds to the colchicine binding site of tubulin.
Asunto(s)
Antineoplásicos/farmacología , Chalconas/farmacología , Naftalenos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Antineoplásicos/metabolismo , Sitios de Unión , Línea Celular Tumoral , Chalconas/síntesis química , Chalconas/química , Chalconas/metabolismo , Ensayos de Selección de Medicamentos Antitumorales , Puntos de Control de la Fase G2 del Ciclo Celular/efectos de los fármacos , Humanos , Simulación del Acoplamiento Molecular , Simulación de Dinámica Molecular , Estructura Molecular , Naftalenos/síntesis química , Naftalenos/química , Naftalenos/metabolismo , Unión Proteica , Relación Estructura-Actividad , Tubulina (Proteína)/química , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/síntesis química , Moduladores de Tubulina/química , Moduladores de Tubulina/metabolismo , Moduladores de Tubulina/farmacologíaRESUMEN
Ganoderma mushrooms are of great nutritious and medicinal values. This study was designed to characterize compounds from the fruiting bodies of Ganoderma cochlear and investigate their protective effects against kidney disorders. Six novel meroterpenoids cochlearoids F-K (1-6) were isolated by utilizing phytochemical approaches. Their structures were identified on the basis of extensive spectroscopic data and calculation methods. Biological evaluation shows that compounds 1-4 and 6 exhibit potent inhibitory activity on fibronectin overproduction in TGF-ß1-induced HKC-8 cells.
Asunto(s)
Cuerpos Fructíferos de los Hongos/química , Ganoderma/química , Riñón/efectos de los fármacos , Sustancias Protectoras/farmacología , Terpenos/química , Terpenos/farmacología , Línea Celular , Fibronectinas/metabolismo , Humanos , Riñón/metabolismo , Terpenos/aislamiento & purificación , Factor de Crecimiento Transformador beta1/metabolismoRESUMEN
The morphological characteristic of Dendrobium moschatum (Buch.-Ham.) Sw. 1805 is very distinctive among Dendrobium Sw. 1799, and it has high medicinal and ornamental values. Here, we reported the first complete chloroplast genome of D. moschatum. The complete genome of D. moschatum was 159,701 bp in length with 130 genes, including 38 tRNA, 8 rRNA, and 84 protein-coding genes. Phylogenetic analysis showed that D. moschatum was strongly allied with D. denneanum Kerr. 1933.
RESUMEN
Nine multifarious new meroterpenoids, cochlearols E-M (1-9), along with seven known meroterpenoids 10-16, were isolated from the fruiting bodies of Ganoderma cochlear. Racemic 1, 6-8, 10 and 13 were separated by chiral HPLC. The structures were elucidated based on detailed spectroscopic analyses (HRESIMS, 1D/2D-NMR) and calculated electronic circular dichroism (ECD). Their biological activities against renal fibrosis were evaluated by using rat normal and diseased renal interstitial fibroblast cells (NRK49F). The results show that compounds 7a, 7b, and 10a exhibit potent proliferation inhibition in TGF-ß1-induced NRK-49F cells.
Asunto(s)
Fibroblastos/efectos de los fármacos , Ganoderma/química , Terpenos/farmacología , Animales , Línea Celular , China , Fibrosis , Cuerpos Fructíferos de los Hongos/química , Riñón/citología , Estructura Molecular , Ratas , Terpenos/aislamiento & purificaciónRESUMEN
Twelve previously undescribed phenolic meroterpenoids, cochlearols N-Y, along with two known analogs, ganocochlearins B and C, were isolated from the fruiting bodies of Ganoderma cochlear. Most of these substances were isolated as racemic mixtures. The structures of cochlearols N-Y were assigned based upon spectroscopic data and theoretical calculations. The renoprotective activities of these compounds were evaluated using normal and diseased rat renal interstitial fibroblast cells (NRK-49F). The results show that ganocochlearins S, U, X and Y display potent inhibitory activities against fibronectin overproduction in TGF-ß1-induced NRK-49F cells.
Asunto(s)
Citoprotección/efectos de los fármacos , Ganoderma/química , Riñón/citología , Fenoles/química , Terpenos/química , Terpenos/farmacología , Animales , Línea Celular , Cuerpos Fructíferos de los Hongos/química , Riñón/efectos de los fármacos , Modelos Moleculares , Conformación Molecular , RatasRESUMEN
OBJECTIVE: To explore which areas of health-related quality of life were affected in Chinese patients, and to identify whether the areas are well covered by validated questionnaires. DESIGN: A qualitative study based on semistructured interviews was conducted. A qualitative thematic analysis following the approach of Colaizzi was used to analyse the interview data for significant statements and phrases. The themes and subthemes organised from the analysis were then compared by using the following current instruments: National Eye Institute Visual Function Questionnaire (NEI-VFQ-25), Macular Disease Quality of life Questionnaire (MacDQoL) and Low-Luminance Questionnaire (LLD). PARTICIPANTS AND SETTING: Twenty-one patients with age-related macular degeneration were recruited from the eye clinic of Southwest Eye Hospital in Chongqing, mainland China. RESULTS: The mean age of the participants was 69.8 years (range 57-82 years) and the duration of the disease ranged from 3 months to 6 years. The qualitative analysis revealed nine important domains including symptoms, difficulties with daily activities, depending on others, depression and uncertainty, optimism and hope, social isolation, role change, family support and financial burden. However, all the three questionnaires were insufficient to capture the full extent of quality of life issues of Chinese patients with AMD, and MacDQoL covered more domains when compared with NEI-VFQ-25 and LLD. CONCLUSION: The domains of concepts important to people with AMD in the Chinese culture are not fully represented in the three widely used questionnaires. Nine important domains were identified for the assessment of quality of life and should be considered when assessing the impact of AMD on Chinese individuals. Further studies are needed to develop an AMD quality of life questionnaire, better tailored to the needs and culture of Chinese patients.
Asunto(s)
Degeneración Macular , Calidad de Vida , Anciano , Anciano de 80 o más Años , China , Femenino , Humanos , Degeneración Macular/complicaciones , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Agudeza VisualRESUMEN
Several carbonaceous mesocellular foams (C-MCFs) were prepared with MCF-silica as template using the carbon precursors of sucrose, furfuryl alcohol and lab-made phenolic resin, and the corresponding C-MCFs were named as C-MCF-Suc, C-MCF-FA and C-MCF-PR, respectively. The results of SEM, transmission electron microscopy, N2 adsorption-desorption and energy-dispersive X-ray measurements indicated that the C-MCFs prepared from different carbon source appeared morphologically with different degree of order and different pore distribution. The C-MCF-FA exhibited the highest ordered structure and the smallest pore distribution among the foams. The optimum conditions for adsorption of C-MCFs on glucose oxidase (GOD) were also studied, and the maximum adsorbance was determined. The adsorption of GOD on C-MCF-FA was performed at different pH with different GOD concentrations. The maximum adsorption (423.3 mg g(-1)) was observed near the isoelectric point of the GOD (pI ≈ 5.0) with a GOD concentration of 6.0 mg mL(-1), suggesting that the GOD adsorption on C-MCFs might be affected strongly by the electric repulsion between the GOD molecules. Moreover, GOD adsorption performances on different C-MCFs revealed that both the pore size and the pore volume played important roles in the adsorption process, and the window size of C-MCFs dominated the residual immobilized amounts of GOD. Compared to the other two C-MCFs, the C-MCF-FA with a smaller window pore (10 nm) and higher volume (1.40 cm(3) g(-1)) exhibited the highest GOD adsorption and catalytic activity. Furthermore, the immobilized GOD exhibited improved thermal and storable stabilities. Thus the C-MCF-FA could be served as the prospective GOD carrier material used in enzymatic fuel cells.
Asunto(s)
Carbono/química , Carbono/metabolismo , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Adsorción , Formaldehído/química , Furanos/química , Concentración de Iones de Hidrógeno , Fenoles/química , Polímeros/química , Porosidad , Dióxido de Silicio/química , Sacarosa/químicaRESUMEN
T-type calcium channel (TTCC) inhibitors hold great potential for the treatment of a variety of neurological disorders. Cochlearoids A-E (1-5), five pairs of dimeric meroterpenoid enantiomers, and cochlearines A (6) and B (7), two pairs of enantiomeric hybrid metabolites, were isolated and characterized from Ganoderma cochlear. Biological evaluation found that compounds (+)-1, (-)-3, and (±)-6 significantly inhibited Cav3.1 TTCC and showed noticeable selectivity against Cav1.2, Cav2.1, Cav2.2, and Kv11.1 (hERG) channels.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio Tipo N/química , Canales de Calcio Tipo T/química , Ganoderma/química , Inhibición Neural/efectos de los fármacos , Terpenos/síntesis química , Terpenos/farmacología , Bloqueadores de los Canales de Calcio/química , Canales de Calcio Tipo N/metabolismo , Canales de Calcio Tipo T/metabolismo , Humanos , Estructura Molecular , Inhibición Neural/fisiología , Terpenos/químicaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Several Ganoderma fungi are well-known for their medical uses to treat cancer, insomnia and kidney disease in East Asia. Triperpenoids and polysaccharides have been considered for a long time to be the major active components of the genus Ganoderma. The present study is to examine the effects of lingzhilactones from G. lingzhi on adriamycin-induced nephropathy in mice. MATERIALS AND METHODS: A combination of various chromatography led to the isolation of lingzhilactones A-C, their structures were identified by spectroscopic and computational methods. The intracellular reactive oxygen species (ROS) was detected with the carboxymethyl-H2-dichlorofluorescein diacetate fluoroprobe. The fibrotic markers were analyzed by real-time RT-PCR and Western blot analyses. Detection of SEAP was conducted with the chemiluminescent. Urine albumin was measured using an ELISA assay. Histology and immunohistochemical staining was used to assess fibrotic lesions in mice. RESULTS: Three new lingzhilactones A-C (1-3) containing a fused lactone moiety were isolated from G. lingzhi. We found that 2 could inhibit ROS generation in a dose-dependent manner, inhibit mRNA expression of collagen IV, fibronectin, IL-6 and increase expression of Nrf2 in rat tubular epithelial cells. Furthermore, we found that 2 could reduce urinary albumin levels, abrogate myofibroblastic activation and inhibit the phosphorylation of Smad3 in adriamycin-induced mice. CONCLUSIONS: The in vitro and in vivo results suggested that lingzhilactone B could protect against renal injuries by increasing the activities of antioxidants and inhibiting inflammation. The inhibition of Smad3 phosphorylation suggested that this substance displays in vivo antifibrotic activity by a mechanism that is dependent on disruption of Smad3. These results promote understanding of the traditional usage of G. lingzhi and provide promising findings which may be beneficial for anti-kidney disease drug design.
Asunto(s)
Antiinflamatorios/uso terapéutico , Ganoderma , Enfermedades Renales/tratamiento farmacológico , Lactonas/uso terapéutico , Animales , Antiinflamatorios/aislamiento & purificación , Antiinflamatorios/farmacología , Línea Celular , Colágeno Tipo IV/genética , Doxorrubicina , Fibronectinas/genética , Interleucina-6/genética , Enfermedades Renales/inducido químicamente , Enfermedades Renales/metabolismo , Lactonas/aislamiento & purificación , Lactonas/farmacología , Masculino , Células Mesangiales/efectos de los fármacos , Células Mesangiales/metabolismo , Ratones , Ratones Endogámicos BALB C , Factor 2 Relacionado con NF-E2/genética , ARN Mensajero/metabolismo , Ratas , Especies Reactivas de Oxígeno/metabolismo , Proteína smad3/genética , Proteína smad3/metabolismoRESUMEN
(+)- and (-)-cochlearols A (1) and B (2), two meroterpenoids with novel polycyclic skeletons, were isolated from the fruiting bodies of the fungus Ganoderma cochlear. Their structures and stereochemistry were determined by using spectroscopic, computational and single-crystal X-ray diffraction methods. Cochlearol A is a new normeroterpenoid containing a naturally unusual dioxaspiro[4.5]decane motif. Biological studies showed that (-)-2 is a strong inhibitor of p-Smads, exhibiting renoprotective activities in TGF-ß1 induced rat renal proximal tubular cells.