2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 56-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes

摘要

2-O-Acyl-3-O-(1-acyloxyalkyl) prodrug derivatives, >15, of 5,6-isopropylidene-l-ascorbic acid, >VCA, and l-ascorbic acid, >VC, have been characterized by measuring (1) their solubilities in water (SAQ) and in 1-octanol (SOCT); (2) the ability of one member of the homologous series, >15a, to diffuse through a silicone membrane from its application in propylene glycol:water (PG:AQ), 30:70; (3) the ability of another member of the series, >15e, to express cellular antioxidant activity (CAA) in HaCaT cells; and (4) the ability of >15e to support cell viability in HaCaT cells. All of the prodrugs were more soluble in 1-octanol than >VC or >VCA were. >15a, which exhibited a good balance between SOCT and SAQ, was found to deliver approximately 15 times more >15a than >VCA delivered >VCA through a silicone membrane from PG:AQ, 30:70. Under those conditions, no >VC permeated the membrane. >15e, which hydrolyzed to release acetaldehyde as a byproduct instead of the toxin formaldehyde, exhibited approximately 30 times the antioxidant activity of >VC in CaHaT cells and supported cell viability up to 900 μM in HaCaT cells.