title: 2-O-Acyl-3-O-(1-acyloxyalkyl) Prodrugs of 5,6-Isopropylidene-l-Ascorbic Acid and l-Ascorbic Acid: Antioxidant Activity and Ability to Permeate Silicone Membranes.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA. nthiele@ufl.edu.
authors.forename: Nikki A
authors.initials: NA
authors.lastname: Thiele
authors.affiliation: Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA. jmm381@case.edu.
authors.forename: Jennifer
authors.initials: J
authors.lastname: McGowan
authors.affiliation: Department of Medicinal Chemistry, University of Florida, P.O. Box 100485, Gainesville, FL 32610, USA. sloan@cop.ufl.edu.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Sloan
keywords: ">l-ascorbic acid; cellular antioxidant activity; cytotoxicity; prodrugs; soft alkyl; solubilities; topical delivery; vitamin C