The objective of this project was to synthesize and evaluate the antioxidant activity of new topical carbamate (a-TOC-CARB; d-TOC-CARB) co-drugs and their metabolites (tocopherol (TOC) and lipoylamine (LAM) for protection of skin against oxidative damage. Carbamate co-drugs were synthesized from the isocyanate of lipoic acid, which was then coupled to a- or d-TOC. The inhibitory activity of these antioxidants (AO) against lipid peroxidation (LP) using porcine skin as the lipid substrates in the thiobarbituric acid reactive substances (TBARS) assay was determined. IC?50 values for a-TOC (32�M), d-TOC (82�M), and LAM (527�M) were determined. The potencies of a-TOC and d-TOC were consistent with values previously reported for these AO, however the potency of LAM was significantly greater than that observed for LA or LOH. Synergistic antioxidant activity was observed between a-TOC and LAM (IC50 =2.78�M) and d-TOC with LAM (IC50=210.3�M) (hydrolysis products of the co-drugs). The potency of the co-drugs was greater than expected for a-TOC-CARB and d-TOC-CARB, suggesting the co-drugs hydrolyzed during the assay. a- and d-TOC were potent inhibitors of LP. LAM was also found to inhibit LP, which has previously not been reported. Synergistic activity was observed for both a-TOC and d-TOC with LAM. These data suggest that these carbamate co-drugs are excellent candidates for use as topical agents to protect the skin against oxidative damage.

Carbamate co-drugs: Synthesis and inhibition of lipid peroxidation in skin

247th National Meeting (2014)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.