L-Lysine Pro-Prodrug Containing trans-Ferulic Acid for 5-Amino Salicylic Acid Colon Delivery

• Published in: Chemical & pharmaceutical bulletin Vol. 58; no. 1; p. 103
• Main Authors: Cassano, Roberta, Trombino, Sonia, Cilea, Alessia, Ferrarelli, Teresa, Muzzalupo, Rita, Picci, Nevio
• Format: Journal Article
• Language: English
• Published: Tokyo Japan Science and Technology Agency 01.01.2010
• ISSN: 0009-2363; 1347-5223

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 [straight epsilon]-position, we inserted trans-ferulic acid in [straight 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 1H-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.