RESUMEN
Soy isoflavones exhibit various biological activities, such as antioxidant, anti-tumor, anti-inflammatory, and cardiovascular protective effects. The present study was designed to investigate the effects of sixteen synthesized 3-amino-2-hydroxypropoxy genistein derivatives on cell proliferation and activation of Nrf2 (Nuclear factor erythroid 2-related factor 2)/ARE (antioxidant response elements) pathway in human cancer cell lines. Most of the tested compounds exerted greater cytotoxic activity than genistein, as measured by MTT assay. Moreover, compound 8c showed the highest ARE-luciferase reporter activity among the test compounds. It strongly promoted Nrf2 nuclear translocation and up-regulated the expression of total Nrf2 and downstream targets NQO-1 and HO-1 at protein level. The present study may provide a basis for the application of isoflavone derivatives as Nrf2/ARE pathway inducers for cancer therapy and cancer prevention.
Asunto(s)
Genisteína/uso terapéutico , Glycine max/química , Neoplasias/tratamiento farmacológico , Elementos de Respuesta Antioxidante , Línea Celular Tumoral , Proliferación Celular , Genisteína/síntesis química , Genisteína/farmacología , Hemo-Oxigenasa 1/metabolismo , Humanos , Isoflavonas , Factor 2 Relacionado con NF-E2/metabolismo , Neoplasias/metabolismo , Transducción de Señal , Regulación hacia ArribaRESUMEN
Soy isoflavones exert a wide variety of biological activities, such as antioxidant, anti-inflammatory and anti-cancer properties. Nuclear factor erythroid 2-related factor 2 (Nrf2), a bZip transcription factor, plays a key role in soy isoflavones induced protection against oxidative stress and cancer. To obtain more effective isofavones, a series of 7,4'-bis-(3-amino-2-hydroxypropoxy), 7 or 4'-(3-amino-2-hydroxypropoxy) isoflavone derivatives have been synthesized as potential antitumor agents and Nrf2/ARE (antioxidant response element) activators. The cytotoxicity of these compounds in human cancer cell lines MDA-MB-231, HT-29, HCT116, HepG2 and 7402 was tested by MTT assay. In this study, the cytotoxicity of compound 3b exhibited highest cytotoxic activity and at the safety dose range, it also strongly up-regulated antioxidant response element (ARE)-luciferase reporter activity. In addition, compound 3b induced Nrf2 nuclear translocation and upregulated its downstream target genes NQO-1 and HO-1 at protein level. Taken together, our results suggest that compound 3b could be a potential agent for cancer themotherapy or cancer chemoprevention.
Asunto(s)
Antineoplásicos Fitogénicos/síntesis química , Antineoplásicos Fitogénicos/farmacología , Isoflavonas/síntesis química , Isoflavonas/farmacología , Antineoplásicos Fitogénicos/química , Línea Celular Tumoral , Expresión Génica/efectos de los fármacos , Humanos , Isoflavonas/química , Estructura Molecular , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
New chiral Ru(II) complexes delta and lambda-[Ru(bpy)(2)(pyip)](PF(6))(2) [(bpy = 2,2'-bipyridine; pyip = (2-(1-pyrenyl)-1H-imidazo[4,5-f] [1,10]phenanthroline] were synthesized and characterized by elemental analysis, (1)H NMR, ESI-MS, IR, and CD spectra. Their DNA-binding properties were studied by means of UV-vis, emission spectra, CD spectra and viscosity measurements. A subtle but detectable difference was observed in the interaction of both enantiomer with CT-DNA. Spectroscopy experiments indicated that each of these complexes could interact with the DNA. The DNA-binding of the Delta-enantiomer was stronger than that of Lambda-enantiomer. DNA-viscosity experiments provided evidence that both Delta- and Lambda-[Ru(bpy)(2)(pyip)](PF(6))(2) bound to DNA by intercalation. At the same time, the DNA-photocleavage properties of the complexes were investigated too. Under irradiation with UV light, Ru(II) complexes showed different efficiency of cleaving DNA.
Asunto(s)
ADN/metabolismo , Compuestos Organometálicos/síntesis química , Compuestos Organometálicos/metabolismo , Animales , Bovinos , Dicroismo Circular , ADN Superhelicoidal/metabolismo , Desoxirribonucleasas/metabolismo , Electrones , Compuestos Organometálicos/química , Fotólisis , Espectrometría de Fluorescencia , Estereoisomerismo , ViscosidadRESUMEN
The centrosymmetric organic molecule in the title compound, C(10)H(10)N(8)·2H(2)O, is essentially flat and has a trans configuration. The mol-ecules are linked by inter-molecular O-Hâ¯N, N-Hâ¯O and N-Hâ¯N hydrogen bonds to form a linear chain structure.