ABSTRACT
The reaction of the flavonol 3,7,3', 4'-tetra-O-methylquercetin (1) and of the isoflavone 7,4'-di-O-methylgenistein (2) with alkaline iodine in methanol afforded four new iodine derivatives: 8-iodo-5-hydroxy-3,7,3', 4'-tetramethoxy- flavone (1a) and 6-iodo-5-hydroxy-3,7,3', 4'-tetramethoxyflavone (1b) from 1; 2 afforded a mixture of two compounds, identified as a racemic mixture of (±)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-8-iodo-isoflavanone (2a) and (±)-trans-5-hydroxy-2,3,7,4'-tetramethoxy-6,8-diiodo-isoflavanone (2b). The formation of these different products reveals a significant difference involving the chemical interaction between the reactive site of α, β-unsaturated ketones of flavonol and isoflavone under the tested reaction conditions (using I2/KOH/MeOH). Furthermore, the trans stereo selectivity is noteworthy in the nucleophylic addition of methanol at the isoflavone α, β-unsaturated system. The structures were identified on the basis of spectral data, mainly 1D and 2D NMR and mass spectra.
A reação do flavonol 3,7,3',4'-tetra-O-metilquercetina (1) e da isoflavona 7,4'-di-O-metilgenisteina (2) com iodo/KOH em metanol forneceu como produto quatro derivados iodados: 8-iodo-5-hidroxi-3,7,3',4'-tetrametoxiflavona (1a) e 6-iodo-5-hidroxi-3,7,3',4'-tetrametoxiflavona (1b) a partir da iodação de 1; a partir de 2 foi obtida uma mistura racêmica composta de (±)-trans-5-hidroxi-2,3,7,4'-tetrametoxi-8-iodo-isoflavanona (2a) e (±)-trans-5-hidroxi-2,3,7,4'-tetrametoxi-6,8-diiodo-isoflavanona (2b). A formação destes diferentes produtos revela a significante diferença envolvendo a interação química entre o sitio reativo de cetonas α, β-insaturadas de flavonol e de isoflavonas nas condições experimentais testadas (usando I2/KOH/MeOH). Além disso, ressalta-se a estereosseletividade trans na adição de metanol ao sistema α, β-insaturado da isoflavona. As estruturas foram identificadas com análise nos dados espectrométricos de RMN 1D e 2D e massas.
Subject(s)
Flavonoids/chemistry , Iodine/chemistry , Isoflavones/chemistry , Spectrum AnalysisABSTRACT
During carcinogenesis, NF-kappaB mediates processes associated with deregulation of the normal control of proliferation, angiogenesis, and metastasis. Thus, suppression of NF-kappaB has been linked with chemoprevention of cancer. Accumulating findings reveal that heat shock protein 90 (HSP90) is a molecular chaperone and a component of the IkappaB kinase (IKK) complex that plays a central role in NF-kappaB activation. HSP90 also stabilizes key proteins involved in cell cycle control and apoptosis signaling. We have determined whether the exogenous administration of isoflavone-deprived soy peptide prevents 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced rat mammary tumorigenesis and investigated the mechanism of action. Dietary administration of soy peptide (3.3 g/rat/day) significantly reduced the incidence of ductal carcinomas (50%), the number of tumors per multiple tumor-bearing rats (49%; P < 0.05), and extended the latency period of tumor development (8.07 +/- 0.92 weeks) compared to control diet animals (10.80 +/- 1.30; P < 0.05). Our results have further demonstrated that soy peptide (1) dramatically inhibits the expression of HSP90, thereby suppressing signaling pathway leading to NF-kappaB activation; (2) induces expression of p21, p53, and caspase-3 proteins; and (3) inhibits expression of VEGF. In agreement with our in vivo data, soy peptide treatment inhibited the growth of human breast MCF-7 tumor cells in a dose-dependent manner and induced apoptosis. Taken together, our in vivo and in vitro results suggest chemopreventive and tumor suppressive functions of isoflavone-deprived soy peptide by inducing growth arrest and apoptosis.
Subject(s)
Animals , Female , Humans , Rats , 9,10-Dimethyl-1,2-benzanthracene , Adenocarcinoma/prevention & control , Apoptosis/drug effects , Breast Neoplasms/chemically induced , Cell Line, Tumor , Chemoprevention , Gene Expression Regulation, Neoplastic , HSP90 Heat-Shock Proteins/genetics , Isoflavones/chemistry , NF-kappa B/genetics , Peptides/chemistry , Rats, Sprague-Dawley , Soybean Proteins/chemistry , Glycine max/chemistryABSTRACT
A utilização de produtos naturais e suplementos contendo extratos secos de isoflavonas aumentou na última década, devido, principalmente, aos efeitos benéficos atribuídos a estes compostos no alívio dos sintomas da menopausa. Genisteína, daidzeína e gliciteína são as agliconas mais abundantes nos extratos de soja, ocorrendo também como glicosídeos. Tendo em vista seus usos, não existe ainda na literatura uma definição da quantidade mínima de cada uma das agliconas que os extratos ou cápsulas de isoflavonas devem ter, e também não existe um método oficial para o controle de qualidade dos mesmos. O presente trabalho apresenta um método por CCD para análise qualitativa das três agliconas e de seus glicosídeos em extratos e cápsulas de isoflavonas, antes e após hidrólise ácida. A análise quantitativa das cápsulas de isoflavonas, realizada por cromatografia líquida de alta eficiência (CLAE), revelou grandes variações nos teores das três agliconas, após hidrólise ácida. Os teores variaram da seguinte forma, nos 18 lotes de cápsulas avaliados: daidzeína (13,34 a 76,20 mg/cápsula), genisteína (0,61 a 27,18 mg/cápsula) e gliciteína (0,49 a 8,80 mg/cápsula).
The use of herbal products and supplements based on isoflavone dry extracts has increased considerably in the last decade, mainly due to beneficial effects to relief of the menopausal symptoms credited to those compounds. Genistein, daidzein and glycitein are the most abundant isoflavone aglycones found in soy extract, where they also occur as glycosides. Concerning their uses, there is neither standardization regarding the minimum content of each aglycone in the extracts or capsules, nor an official method to the quality control of these products. The present work presents a TLC method for qualitative analysis of the three aglycones and their glycosides in extracts and capsules of isoflavones, before and after acid hydrolysis. The quantitative analysis of the isoflavone capsules, carried out by high performance liquid chromatography (HPLC), showed high variation in the content of the three aglycones, after acid hydrolysis. The contents varied in the following way, in the 18 batches of evaluated capsules: daidzein (13.34 to 76.20 mg/capsule), genistein (0.61 to 27.18 mg/capsule) and glycitein (0.49 to 8.80 mg/capsule).
Subject(s)
Chromatography, High Pressure Liquid , Chromatography, Thin Layer , Isoflavones/chemistryABSTRACT
Efetuou-se revisão da literatura sobre os recentes progressos na pesquisa com isoflavonas,a bordando os principais aspectos da bioquímica e fisiologia desses compostos, além de destacar seus efeitos para a saúde. Diversos estudos apontam para a capacidade das isoflavonas em prevenir e/ou tratar doenças crônico-degenerativas como a osteoporose, câncer e doenças coronarianas, entre outras. No entanto, diversas questões ainda devem ser respondidas e novos estudos (com animais e humanos) necessitam ser realizados a fim de esclarecer seu verdadeiro mecanismo de ação, bem como os benefícios das isoflavonas para o organismo