L-lysine Pro-prodrug containing trans-ferulic acid for 5-amino salicylic acid colon delivery: Synthesis, characterization and in vitro antioxidant activity evaluation

In the present work, we report the synthesis of a new 5-amino salicylic acid (5-ASA) pro-prodrug, useful in Crohn disease treatment, and the evaluation of its antioxidant activity. Using as pharmacological carrier L-lysine amino acid and taking advantage of its intrinsic chemical reactivity, due to the presence of two amino groups, placed on the chiral center and in epsilon-position, we inserted trans-ferulic acid in epsilon-position, through amidation reaction, esterified with methanol the carboxylic group and, finally, submitted the free amino group to diazotation with 5-ASA, principal drug for inflammatory bowel diseases (IBD) care. All intermediates of synthesis and the final product (derivative A) were characterized with usual spectroscopic techniques, as FT-IR, GC/MS and (1)H-MNR. Finally, the derivative A antioxidant activity in inhibiting the lipid peroxidation, in rat-liver microsomal membranes, induced in vitro by two different sources of free radicals, 2,2'-azobis (2-amidinopropane) (AAPH) and tert-butyl hydroperoxide (tert-BOOH), was evaluated. Our pro-prodrug could be successfully applied in pharmaceutical field both as prodrug of 5-ASA than as carrier of trans-ferulic acid.