RESUMEN
Inflammation is a key mediator in the progression of atherosclerosis (AS). Benzoinum, a resin secreted from the bark of Styrax tonkinensis, has been widely used as a form of traditional Chinese medicine in clinical settings to enhance cardiovascular function, but the active components of the resin responsible for those pharmaceutical effects remain unclear. To better clarify these components, a new phenylpropane derivative termed stybenpropol A was isolated from benzoinum and characterized via comprehensive spectra a nalysis. We further assessed how this phenylpropane derivative affected treatment of human umbilical vein endothelial cells (HUVECs) with tumor necrosis factor-α (TNF-α). Our results revealed that stybenpropol A reduced soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) expression by ELISA, inhibited apoptosis, and accelerated nitric oxide (NO) release in TNF-α-treated HUVECs. We further found that stybenpropol A decreased VCAM-1, ICAM-1, Bax, and caspase-9 protein levels, and increased the protein levels of Bcl-2, IKK-ß, and IκB-α. This study identified a new, natural phenylpropane derivative of benzoinum, and is the first to reveal its cytoprotective effects in the context of TNF-α-treated HUVECs via regulation of the NF-κB and caspase-9 signaling pathways.
Asunto(s)
Antiinflamatorios/farmacología , Benzoína/farmacología , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Aterosclerosis/metabolismo , Basidiomycota/química , Benzoína/química , Caspasa 9/metabolismo , Molécula 1 de Adhesión Celular/metabolismo , Humanos , Quinasa I-kappa B/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Interleucina-1beta/metabolismo , Interleucina-8 , Inhibidor NF-kappaB alfa/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Transducción de Señal/efectos de los fármacos , Factor de Transcripción ReIA/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Reverse micelles (RMs) with confined water pools have been applied in many fields. However, the water insolubility of RMs seriously limits the scope of their application, especially those needed to operate in aqueous environments. Here, we report the first successful transfer of RMs from the organic phase to water phase without disturbing their confined water pools and hydrophobic alkyl region. This transfer was achieved by virtue of a mild host-guest interaction between the hydrophobic tails of interfacial cross-linked reverse micelles (ICRMs) and the hydrophobic cavity of (2-hydroxypropyl)-ß-cyclodextrin (HP-ß-CD). Benefitting from the maintained confined water pools and the hydrophobic scaffold, the obtained water-soluble ICRMs served as multifunctional nanoplatforms for enzyme-mimicking catalysis and image-guided cancer therapy, which were impossible for normal RMs lacking water solubility or confined pool-buried water-soluble nanoparticles without a hydrophobic alkyl chain. This mild transfer approach thus surmounts the application obstacle of RMs and opens up new avenues for their application in aqueous environments.
Asunto(s)
Antineoplásicos/farmacología , Portadores de Fármacos/química , Colorantes Fluorescentes/química , Nanopartículas del Metal/química , Micelas , 2-Hidroxipropil-beta-Ciclodextrina/química , Células A549 , Benzoína/química , Catálisis , Portadores de Fármacos/síntesis química , Liberación de Fármacos , Fluorouracilo/análogos & derivados , Fluorouracilo/farmacología , Oro/química , Humanos , Neoplasias/diagnóstico por imagen , Neoplasias/tratamiento farmacológico , Oxidación-Reducción , Rodaminas/química , Agua/químicaRESUMEN
Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD) were discovered in improving hyperuricemia and acute gouty arthritis. In vitro studies revealed that most compounds not only suppressed XOD activity, but blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like receptor 4 (TLR4) signaling pathway. More importantly, (E)-1-(6-methoxybenzo[d]oxazol-2-yl)-2-(4-methoxyphenyl)ethanone oxime (5d) exhibited anti-hyperuricemic and anti-acute gouty arthritis activities through regulating XOD, NLRP3 and TLR4. Compound 5d may serve as a tool compound for further design of anti-gout drugs targeting both innate immune sensors and XOD.
Asunto(s)
Aminas/farmacología , Inhibidores Enzimáticos/farmacología , Supresores de la Gota/farmacología , Gota/tratamiento farmacológico , Oximas/farmacología , Xantina Oxidasa/antagonistas & inhibidores , Aminas/síntesis química , Aminas/química , Animales , Benzoína/análogos & derivados , Benzoína/química , Benzoína/farmacología , Benzoxazoles/química , Benzoxazoles/farmacología , Línea Celular , Relación Dosis-Respuesta a Droga , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Supresores de la Gota/síntesis química , Supresores de la Gota/química , Células HEK293 , Humanos , Inmunidad Innata/efectos de los fármacos , Hígado/enzimología , Masculino , Ratones , Ratones Endogámicos , Estructura Molecular , Oximas/síntesis química , Oximas/química , Ratas , Ratas Sprague-Dawley , Relación Estructura-Actividad , Ácido Úrico/sangre , Xantina Oxidasa/metabolismoRESUMEN
Eight new C-4-alkylated deoxybenzoins (1-8), three new diphenylethylenes (9-11), and five known diphenylethylenes were isolated from Arundina graminifolia. The structures of 1-11 were elucidated by spectroscopic methods including extensive 1D and 2D NMR techniques. Compounds 9-11 are the first naturally occurring diphenylethylenes possessing a hydroxyethyl unit. Compounds 1-11 were evaluated for cytotoxicity against five human tumor cell lines. Compounds 4, 5, and 9-11 showed significant cytotoxicity against five cancer cell lines, with IC50 values ranging from 1.8 to 8.7 µM.
Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Benzoína/análogos & derivados , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Etilenodiaminas/aislamiento & purificación , Etilenodiaminas/farmacología , Orchidaceae/química , Antineoplásicos Fitogénicos/química , Benzoína/química , Benzoína/aislamiento & purificación , Benzoína/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Etilenodiaminas/química , Humanos , Concentración 50 Inhibidora , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Estilbenos/químicaRESUMEN
A new solid phase extraction method for separation and preconcentration of trace amounts of uranium, thorium, and zirconium in water samples is proposed. The procedure is based on the adsorption of U(VI), Th(IV) and Zr(IV) ions on a column of Amberlite XAD-2000 resin loaded with alpha-benzoin oxime prior to their simultaneous spectrophotometric determination with Arsenazo III using orthogonal signal correction partial least squares method. The enrichment factor for preconcentration of uranium, thorium, and zirconium was found to be 100. The detection limits for U(VI), Th(IV) and Zr(IV) were 0.50, 0.54, and 0.48microgL(-1), respectively. The precision of the method, evaluated as the relative standard deviation obtained by analyzing a series of 10 replicates, was below 4% for all elements. The practical applicability of the developed sorbent was examined using synthetic seawater, natural waters and ceramic samples.
Asunto(s)
Métodos Analíticos de la Preparación de la Muestra/métodos , Benzoína/análogos & derivados , Contaminantes Ambientales/análisis , Contaminantes Ambientales/aislamiento & purificación , Metales Pesados/análisis , Metales Pesados/aislamiento & purificación , Oximas/química , Resinas Sintéticas/química , Extracción en Fase Sólida/métodos , Adsorción , Benzoína/química , Calibración , Compuestos Cromogénicos/química , Contaminantes Ambientales/química , Concentración de Iones de Hidrógeno , Análisis de los Mínimos Cuadrados , Límite de Detección , Metales Pesados/química , Análisis Multivariante , Procesamiento de Señales Asistido por Computador , Espectrofotometría , Torio/análisis , Torio/química , Torio/aislamiento & purificación , Factores de Tiempo , Uranio/análisis , Uranio/química , Uranio/aislamiento & purificación , Circonio/análisis , Circonio/química , Circonio/aislamiento & purificaciónRESUMEN
Furoin, a benzoin analogue, was examined as novel fluorogenic reagent for the selective and sensitive LC determination of various guanidines after pre-column derivatization. The derivatization reaction was carried out at 100 degrees C for 5 min to give adducts that were separated on a Phenomenex Synergi MAX-RP column and detected at lambda(em)=410 nm with lambda(ex)=325 nm. The reagent showed to be useful both for determining together arginine (Arg) and creatine (CT) in dietary supplements under elution isocratic conditions and for the simultaneous analysis of a variety of guanidines in biological samples (human plasma and urine) under elution gradient conditions. The detection limits ranged from 7 to 25 fmol. Recovery studies showed good results for all determined guanidino compounds (85.6-106.2%; R.S.D.=1.1-6.2%).
Asunto(s)
Benzoína/análogos & derivados , Benzoína/química , Cromatografía Liquida/métodos , Guanidinas/análisis , Indicadores y Reactivos/química , Calibración , Suplementos Dietéticos/análisis , Furanos , Guanidinas/sangre , Guanidinas/orina , Humanos , Estructura Molecular , Estándares de Referencia , Sensibilidad y Especificidad , Factores de TiempoRESUMEN
Deoxybenzoins are plant compounds with similar structure to isoflavones. In this study, we evaluated the ability of two synthesized deoxybenzoins (compound 1 and compound 2) (a) to influence the activity of the estrogen receptor subtypes ERalpha and ERbeta in HeLa cells co-transfected with an estrogen response element-driven luciferase reporter gene and ERalpha- or ERbeta-expression vectors, (b) to modulate the IGFBP-3 and pS2 protein in MCF-7 breast cancer cells, (c) to induce mineralization of KS483 osteoblasts and (d) to affect the cell viability of endometrial (Ishikawa) and breast (MCF-7, MDA-MB-231) cancer cells. Docking and binding energy calculations were performed using the mixed Monte Carlo/Low Mode search method (Macromodel 6.5). Compound 1 displayed significant estrogenic activity via ERbeta but no activity via ERalpha. Compound 2 was an estrogen-agonist via ERalpha and antagonist via ERbeta. Both compounds increased, like the pure antiestrogen ICI182780, the IGFBP-3 levels. Compound 2 induced, like 17beta-estradiol, significant mineralization in osteoblasts. The cell viability of Ishikawa cells was unchanged in the presence of either compound. Compound 1 increased MCF-7 cell viability consistently with an increase in pS2 levels, whereas compound 2 inhibited the cell viability. Molecular modeling confirmed the agonistic or antagonistic behaviour of compound 2 via ER subtypes. Compound 2, being an agonist in osteoblasts, an antagonist in breast cancer cells, with no estrogenic effects in endometrial cancer cells, makes it a potential selective estrogen receptor modulator and a choice for hormone replacement therapy.
Asunto(s)
Benzoína/análogos & derivados , Calcificación Fisiológica/efectos de los fármacos , Receptor alfa de Estrógeno/metabolismo , Receptor beta de Estrógeno/metabolismo , Estrógenos/metabolismo , Moduladores Selectivos de los Receptores de Estrógeno/farmacología , Benzoína/síntesis química , Benzoína/química , Benzoína/metabolismo , Benzoína/farmacología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Estradiol/farmacología , Antagonistas de Estrógenos/química , Antagonistas de Estrógenos/metabolismo , Antagonistas de Estrógenos/farmacología , Estrógenos/agonistas , Femenino , Inhibidores de Crecimiento/metabolismo , Humanos , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Método de Montecarlo , Osteoblastos/metabolismo , Fitoestrógenos/metabolismo , Fitoestrógenos/farmacología , Moduladores Selectivos de los Receptores de Estrógeno/química , Moduladores Selectivos de los Receptores de Estrógeno/metabolismo , Factor Trefoil-1 , Proteínas Supresoras de Tumor/metabolismoRESUMEN
Alumina or silica gel are used as catalysts for a solvent-free oxidation of benzoins to the corresponding benzils. These catalysts are easily recovered after completion of the reactions, which are carried out either by heating in a sand bath or using microwave irradiation. Comparison of the results obtained with both catalysts indicates that all the reactants examined were oxidized faster on alumina than on silica under these conditions.
Asunto(s)
Óxido de Aluminio/química , Benzoína/química , Óxidos/química , Fenilglioxal/análogos & derivados , Dióxido de Silicio/química , Solventes/química , Catálisis , Oxidación-Reducción , Fenilglioxal/química , Propiedades de SuperficieRESUMEN
Although deoxybenzoins are intermediates in the synthesis of isoflavones, their estrogenic activity has not been investigated. Eleven deoxybenzoins were synthesized and their estrogenicity was evaluated. While their affinities for estrogen receptors (ER) ERalpha and ERbeta were found grossly comparable to those of daidzein, some exhibited considerable selectivity and transcriptional bias toward ERbeta, which appeared to allow for enhancement of ER-mediated transcription via deoxybenzoin binding of ERbeta. Their activity to stimulate the proliferation of ER-positive breast cancer cells and regulate the expression of endogenous and stably transfected reporter genes differed considerably, with some inhibiting cell proliferation while effectively inducing gene expression at the same time. Molecular modeling confirmed that deoxybenzoins fit well in the ligand binding pocket of ERbeta, albeit with different orientations. Our data support the view that deoxybenzoins constitute a promising new class of ERbeta-biased phytoestrogens.