RESUMO
Effect of nine new derivatives of dihydroquercetin (taxifolin) on the viability of cultivated normal and tumor cells, their antioxidant activity, and interconnection of the antioxidant activity with the chemical structure have been studied. Among these dihydroquercetin derivatives, the maximum antiproliferative activity on the model of rat fibroblast culture exhibited KN-2, KN-4, KN-7, and KN-8 compounds, while KN-7 and KN-8 compounds also showed maximum activity on the model of MCF-7 tumor cell culture (human breast cancer). The maximum general antioxidant activity was observed for the native dihydroquercetin and KN-8 compound. There is a strong correlation (with a correlation coefficient of 0.93) between the antiproliferative effects of dihydroquercetin derivatives on murine skin fibroblasts and MCF-7 cells (human breast cancer).
Assuntos
Antioxidantes/farmacologia , Proliferação de Células/efeitos dos fármacos , Quercetina/análogos & derivados , Animais , Animais Recém-Nascidos , Antioxidantes/química , Medula Óssea/efeitos dos fármacos , Medula Óssea/metabolismo , Técnicas de Cultura de Células , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Peróxidos Lipídicos/metabolismo , Quercetina/química , Quercetina/farmacologia , Ratos , Relação Estrutura-AtividadeRESUMO
The natural flavanoid dihydroquercetin was for the first time regioselectively phosphorylated using phosphoramidites. The resulting compounds were isolated in a homogeneous state as phosphorothioates. The structure of the compounds was confirmed by 1H, 13C, and 31P NMR spectroscopy.
Assuntos
Quercetina/análogos & derivados , Quercetina/química , Flavonóis , Compostos Organofosforados , FosforilaçãoRESUMO
3,5-Cyclic phosphates and phosphoramides of 6-halogenated glucofuranoses were synthesized via interaction of 3,5,6-bicyclophosphites of 1,2-O-alkylidene-alpha-D-glucofuranoses with halogens (followed by treatment with nucleophilic reagents) and N-chloroamines. 3,5-Cyclic trans-dibutylphosphoramides of 6-chloro-6-deoxy-1,2-O-isopropylidene- and 6-chloro-6-deoxy-(R)-(2,2,2)-trichloroethylidene)-alpha-D-glucofuranoses were shown to possess antiproliferative activity against CaOv human ovarian carcinoma cells in vitro (CE50 of approximately 10(-5) M). Cyclic trans-dibutylphosphoramide of 6-chloro-6-deoxy-1,2,-O-isopropylidene-alpha-D-glucofuranose also displayed marked antitumor effect on P-388 transplantable murine leukemia in vivo (the maximum increase in life span of 100% was reached at the quintuple injection of 100 mg/kg daily).
Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Glucofosfatos/síntese química , Leucemia P388/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Divisão Celular/efeitos dos fármacos , Glucofosfatos/farmacologia , Glucofosfatos/uso terapêutico , Leucemia P388/mortalidade , Espectroscopia de Ressonância Magnética , Camundongos , Relação Estrutura-Atividade , Células Tumorais CultivadasAssuntos
Cálcio/metabolismo , Desoxiaçúcares/farmacologia , Desoxiglucose/farmacologia , Ativação Linfocitária , Mitógenos/farmacologia , Linfócitos T/metabolismo , Animais , Bucladesina/farmacologia , Células Cultivadas , AMP Cíclico/metabolismo , Desoxiglucose/análogos & derivados , Corantes Fluorescentes , Concentração de Íons de Hidrogênio , Ratos , Ratos Endogâmicos , Linfócitos T/citologia , Linfócitos T/efeitos dos fármacosRESUMO
1, 2-O-Cyclohexylidene- and 1, 2-O-isopropylidene-alpha-D-glucofuranose react with hexa-alkylphosphorous triamides to give the corresponding 3, 5, 6-phosphites. Treatment of the latter compounds with chlorine and bromine affords 1, 2-substituted 6-deoxy-6-halogeno-alpha-D-glucofuranose 3, 5-phosphorohalogenidates. Replacement of halogen at phsophorus by hydroxyl and amino groups has been investigated. Cyclic phosphorohalogenidates isomerize in N, N-dimethylformamide. The stereochemistry of the compounds investigated was established by using 1H- and 13C-n.m.r. data.
