Isoprenilflavonoides: síntesis y actividad biológica

Abstract

Los prenilflavonoides son compuestos híbridos de terpenoides y flavonoides que, al combinar ambos fragmentos en su estructura, presentan interesantes actividades biológicas como antiparasitarios, anticarcinogénicos, antiinflamatorios... y, últimamente están tomando mucha importancia su actividad como inhibidores de aromatasa y su aplicación en la resistencia a multifármacos. Debido a su interesante perfil de actividad, se ha puesto a punto la alquilación de flavonas y flavonoles con monoterpenos, como geranilo, y diterpenos de esqueleto labdano, obteniendo una gran variedad de híbridos con los que se ha realizado un estudio de su actividad antitumoral. De dicho estudio se concluye que los flavonoides con cadenas prenílicas en C-8 incrementan su actividad, no siendo activas las bases libres.Con objeto de llevar a cabo un estudio de las relaciones estructura-actividad de moléculas más simples, se han sintetizado veintitrés derivados de floroacetofenona alquilados con cadenas de diferente longitud, algunas isoprénicas y otras simplemente lineales con o sin dobles enlaces. Se concluye que la longitud de la cadena es crítica para la actividad, siendo más activos los productos de C-alquilación en el anillo aromático.Se han sintetizado por primera vez dos productos naturales: macarangin e isomacarangin. También se ha llevado a cabo la primera síntesis de (+)-denticulaflavonol, enantiómero del producto natural aislado de Macaranga denticulata, confirmándose así su estructura y determinando su configuración absoluta.Finalmente se ha abierto el camino hacia la síntesis de la ciclohexil chalcona panduratin A, la cual presenta importantes actividades biológicas como antiinflamatorio, anticancerígeno y antivírico.

Prenylflavonoids are hybrids of terpenoids and flavonoids. Due to the presence of both moeities in their framework, they exhibit interesting biological activities such as antiparasitic, anticarcinogenic, anti-inflammatory Lately, their activity as inhibitors of aromatase and their application on multidrug resistence (MDR) studies increase their importance. Due to their wide activity profile, alkylation of flavones and flavonols with monoterpenes, such as geranyl and diterpenes of labdane moiety, has been carried out. A wide variety of hybrids has been synthesised and antitumour activity research work done. It can be concluded that flavonoids prenylated at C-8 increased their activity.In order to carry out a structure-activity relationship (SAR) study of easier synthesised compounds, 23 alkylated acetophenones have been obtained. It can be concluded that the length of the chain is critical for the activity. Moreover, the C-alkylated are the most active compounds.A straightforward synthesis of two natural C-geranylflavonoids: macarangin and its enatiomer, isomacarangin, has been described. The enantiomer of the natural product isolated from Macaranga denticulata, (+)-denticulaflavonol, has been synthesised for the first time, confirming its structure and determining its absolute configuration.Finally, the synthetic pathway to achieve the synthesis of the cyclohexyl chalcone derivative (CCD) panduratin A has been established. Panduratin A has important biological activities such as anti-inflammatory, anticancer and antivirus. studies increase their importance. Due to their wide activity profile, alkylation of flavones and flavonols with monoterpenes, such as geranyl and diterpenes of labdane moiety, has been carried out. A wide variety of hybrids has been synthesised and antitumour activity research work done. It can be concluded that flavonoids prenylated at C-8 increased their activity.In order to carry out a structure-activity relationship (SAR) study of easier synthesised compounds, 23 alkylated acetophenones have been obtained. It can be concluded that the length of the chain is critical for the activity. Moreover, the C-alkylated are the most active compounds.A straightforward synthesis of two natural C-geranylflavonoids: macarangin and its enatiomer, isomacarangin, has been described. The enantiomer of the natural product isolated from Macaranga denticulata, (+)-denticulaflavonol, has been synthesised for the first time, confirming its structure and determining its absolute configuration.Finally, the synthetic pathway to achieve the synthesis of the cyclohexyl chalcone derivative (CCD) panduratin A has been established. Panduratin A has important biological activities such as anti-inflammatory, anticancer and antivirus.