Polyphenols are active compounds of the medicinal plants widely distributed in nature. Despite the few and common biosynthetic origins, polyphenols encompass many subclasses of structurally different entities with a variety of pharmacological properties. Many studies suggests that the mechanisms by which plant polyphenols exert their protective actions against various diseases, in part are due to their redox properties. Silibinin belongs to flavonolignan class and is a major component (approximately 30%) of the Silymarin complex extracted from milk thistle [Silybum marianum (L.) Gaertn. Carduus marianus L., Asteraceae]. Silibinin exists as a mixture of two diastereomers: Silybin A and Silybin B. Silibinin has long been studied for a large variety of pharmacological properties ranging from its antioxidant activity to neuroprotective and antiviral activities. Unfortunately, its in vivo applications are rather hampered by its very low bioavailability mainly due to low water solubility. In an attempt to improve its biological properties and facilitate the in vivo applications, we have developed an efficient strategy for the synthesis of Silibinin modified namely Phosphate-Linked Silibinin dimers (PLSd) in which the Silibinin monomer units are linked by phosphodiester bond (Figure). Exploiting the selective protection of Silibinin’s hydroxyl groups, we carried out a synthetic approach using the phosphoramidite chemistry. Water solubility of dimers, radical scavenger activity as well as their ability to react with reactive oxygen species (ROS) were determined. In particular, dimers reactivity with 1O2 and HO∙ was determined by use of Rose Bengal (RB) and hydrogen peroxide (H2O2) as respective ROS sources. For this purpose, laser flash photolysis (LFP) experiments were coupled with a kinetic competition approach. In addition to scavenging activity, the serum stability and cytoprotective (X/XO assay on HepG2 cells) behavior of dimers were evaluated.
Phosphate-Linked Silibinin dimers (PLSd): Synthesis and Radical Scanvenger Behavior / Romanucci, Valeria; Gravante, Raffaele; DI MARINO, Cinzia; Mailhot, Gilles; Brigante, Marcello; Zarrelli, Armando; DI FABIO, Giovanni. - (2017). (Intervento presentato al convegno EFMC VII International Symposium on Advances in Synthetic and Medicinal Chemistry, Vienna).
Phosphate-Linked Silibinin dimers (PLSd): Synthesis and Radical Scanvenger Behavior
Valeria, Romanucci
;Raffaele, Gravante;Cinzia, Di Marino;Armando, Zarrelli;Giovanni, Di Fabio
2017
Abstract
Polyphenols are active compounds of the medicinal plants widely distributed in nature. Despite the few and common biosynthetic origins, polyphenols encompass many subclasses of structurally different entities with a variety of pharmacological properties. Many studies suggests that the mechanisms by which plant polyphenols exert their protective actions against various diseases, in part are due to their redox properties. Silibinin belongs to flavonolignan class and is a major component (approximately 30%) of the Silymarin complex extracted from milk thistle [Silybum marianum (L.) Gaertn. Carduus marianus L., Asteraceae]. Silibinin exists as a mixture of two diastereomers: Silybin A and Silybin B. Silibinin has long been studied for a large variety of pharmacological properties ranging from its antioxidant activity to neuroprotective and antiviral activities. Unfortunately, its in vivo applications are rather hampered by its very low bioavailability mainly due to low water solubility. In an attempt to improve its biological properties and facilitate the in vivo applications, we have developed an efficient strategy for the synthesis of Silibinin modified namely Phosphate-Linked Silibinin dimers (PLSd) in which the Silibinin monomer units are linked by phosphodiester bond (Figure). Exploiting the selective protection of Silibinin’s hydroxyl groups, we carried out a synthetic approach using the phosphoramidite chemistry. Water solubility of dimers, radical scavenger activity as well as their ability to react with reactive oxygen species (ROS) were determined. In particular, dimers reactivity with 1O2 and HO∙ was determined by use of Rose Bengal (RB) and hydrogen peroxide (H2O2) as respective ROS sources. For this purpose, laser flash photolysis (LFP) experiments were coupled with a kinetic competition approach. In addition to scavenging activity, the serum stability and cytoprotective (X/XO assay on HepG2 cells) behavior of dimers were evaluated.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
