A new class of co-drugs were synthesised by joining antioxidant edaravone with a vasodilating substructure containing NO-donor nitrooxy functions, and characterised for their stability in different media, lipophilicity and permeability profile. The products display good stability in water/co-solvent at different pH. Conversely, they are rapidly metabolised into edaravone and NO-donor moietieswhen incubated in human serum or rat-liver homogenates. In the latter conditions time dependent production of nitrite/nitrate (NOx) occurs. The compounds display wide-ranging lipophilicity. PAMPA studies predict good gastrointestinal absorption for a number of these compounds. The title products are potentially useful for treating ROSrelated conditions accompanied by decreased NO availability.
Synthesis physicochemical profile and PAMPA study of new NO-donor edaravone co-drugs
ROLANDO, Barbara;FILIERI, Andrea;CHEGAEV, Konstantin;LAZZARATO, Loretta;GIORGIS, Marta;FRUTTERO, Roberta;GASCO, Alberto
2012-01-01
Abstract
A new class of co-drugs were synthesised by joining antioxidant edaravone with a vasodilating substructure containing NO-donor nitrooxy functions, and characterised for their stability in different media, lipophilicity and permeability profile. The products display good stability in water/co-solvent at different pH. Conversely, they are rapidly metabolised into edaravone and NO-donor moietieswhen incubated in human serum or rat-liver homogenates. In the latter conditions time dependent production of nitrite/nitrate (NOx) occurs. The compounds display wide-ranging lipophilicity. PAMPA studies predict good gastrointestinal absorption for a number of these compounds. The title products are potentially useful for treating ROSrelated conditions accompanied by decreased NO availability.File | Dimensione | Formato | |
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