RESUMEN
In the search for new agents with estrogenic activity mediated by estrogen receptors (ER), six 6,12-dihydro-1-benzopyrano[3,4-b][1,4]benzothiazin-6-ones 3a-f were synthesized. These compounds were readily prepared by the addition of 2-aminothiophenol 2 to substituted 4-hydroxycoumarin derivatives 1a-e. The estrogenic effect has been evaluated on the proliferation of MCF-7 breast adenocarcinoma cells and the specificity of described compounds was evaluated by the inhibition of their effect by ICI 182,780, an antiestrogenic compound. Among the compounds tested, 6,12-dihydro-3-methoxy-1-benzopyrano[3,4-b][1,4]benzothiazin-6-one 3e and 6,12-dihydro-3-hydroxy-1-benzopyrano[3,4-b][1,4]benzothiazin-6-one 3f exhibited an ER-dependent proliferation and a high binding affinity to ER, but a moderate capacity to activate the transcription of a reporter gene. Their pharmacological profiles are defined by their binding properties and their mechanism of action by computational modelling studies.
Asunto(s)
Benzopiranos/farmacología , Neoplasias de la Mama/patología , Congéneres del Estradiol/síntesis química , Congéneres del Estradiol/farmacología , Tiazinas/farmacología , Benzopiranos/síntesis química , División Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Modelos Moleculares , Unión Proteica , Receptores de Estrógenos/metabolismo , Tiazinas/síntesis química , Activación Transcripcional/efectos de los fármacos , Células Tumorales Cultivadas/efectos de los fármacosAsunto(s)
Biología , Química Clínica , Valores de Referencia , Sociedades Médicas , Femenino , Francia , Humanos , MasculinoRESUMEN
A sample of a reference population was selected from an all-inclusive population by a method based on strict physiological and clinical criteria. Sociological and ethnic factors as well as the biological plasma evaluation of the parents were used as family exclusion parameters. Cholesterol and triacylglycerols were measured in total plasma as well as in each lipoprotein fraction isolated by ultracentrifugation. The values are described as functions of sex and age. Total cholesterol varied little with age and sex. It is higher in girls except for HDL values. The maximum difference between boys and girls (age group 15-19 yrs) is mainly due to LDL-bound cholesterol. Plasma triacylglycerol values are generally higher in girls than in boys, particularly for VLDL. The minimum difference is in the age group 15-19 yrs.