I3C is a very active molecule but it presents limits that often prevent their success. Most common problems are low half-life, due to rapid kidney clearance and to rapid inactivation by metabolic enzymes, instability in water and pH gastric, low molecular weight, low water solubility (7 mg/ml, insoluble in cold water) and low selectivity towards cancer cells. In this paper a series of PEG-Indol-3-carbinol conjugates were synthesized in order to overcome some of the limits of I3C, especially the low molecular weight ones. In particular, some polymeric conjugates were prepared by linking I3C to a PEG550-COOH and HOOC-PEG600-COOH polymer that acts like a carrier. In fact, polymeric conjugation allows to improve drug pharmacokinetic profiles by reducing drug clearance, and protects the drug from enzymatic degradation and can target the linked I3C to tumor tissues. The total antioxidant activity of I3C conjugates was determined by the ABTS and chemiluminescence assays and compared with the values of other antioxidant compounds. In vitro assays showed that the I3C-PEG conjugates have significant anti-inflammatory effects, inhibiting NO release in the LPS-induced J774.A1 murine macrophage cell line.
Antioxidant and anti-inflammatory activity of PEG-indol-3-carbinol conjugates
PICCINELLI, ANNA LISA;RASTRELLI, Luca
2014-01-01
Abstract
I3C is a very active molecule but it presents limits that often prevent their success. Most common problems are low half-life, due to rapid kidney clearance and to rapid inactivation by metabolic enzymes, instability in water and pH gastric, low molecular weight, low water solubility (7 mg/ml, insoluble in cold water) and low selectivity towards cancer cells. In this paper a series of PEG-Indol-3-carbinol conjugates were synthesized in order to overcome some of the limits of I3C, especially the low molecular weight ones. In particular, some polymeric conjugates were prepared by linking I3C to a PEG550-COOH and HOOC-PEG600-COOH polymer that acts like a carrier. In fact, polymeric conjugation allows to improve drug pharmacokinetic profiles by reducing drug clearance, and protects the drug from enzymatic degradation and can target the linked I3C to tumor tissues. The total antioxidant activity of I3C conjugates was determined by the ABTS and chemiluminescence assays and compared with the values of other antioxidant compounds. In vitro assays showed that the I3C-PEG conjugates have significant anti-inflammatory effects, inhibiting NO release in the LPS-induced J774.A1 murine macrophage cell line.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
