RESUMEN

A series of aminoisopropanoloxy derivatives of xanthone has been synthesized and their pharmacological properties regarding the cardiovascular system has been evaluated. Radioligand binding and functional studies in isolated organs revealed that title compounds present high affinity and antagonistic potency for α1-(compound 2 and 8), ß-(compounds 1, 3, 4, 7), α1/ß-(compounds 5 and 6) adrenoceptors. Furthermore, compound 7, the structural analogue of verapamil, possesses calcium entry blocking activity. The title compounds showed hypotensive and antiarrhythmic properties due to their adrenoceptor blocking effect. Moreover, they did not affect QRS and QT intervals, and they did not have proarrhythmic potential at tested doses. In addition they exerted anti-aggregation effect. The results of this study suggest that new compounds with multidirectional activity in cardiovascular system might be found in the group of xanthone derivatives.

Asunto(s)

Antagonistas Adrenérgicos/síntesis química , Diseño de Fármacos , Xantonas/química , Antagonistas Adrenérgicos/metabolismo , Antagonistas Adrenérgicos/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/síntesis química , Bloqueadores de los Canales de Calcio/metabolismo , Bloqueadores de los Canales de Calcio/farmacología , Canales de Calcio/química , Canales de Calcio/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Concentración 50 Inhibidora , Masculino , Agregación Plaquetaria/efectos de los fármacos , Ensayo de Unión Radioligante , Ratas , Ratas Wistar , Receptores Adrenérgicos alfa/química , Receptores Adrenérgicos alfa/metabolismo , Receptores Adrenérgicos beta/química , Receptores Adrenérgicos beta/metabolismo , Relación Estructura-Actividad , Verapamilo/química , Xantonas/metabolismo , Xantonas/farmacología