Colon-specific mutual amide prodrugs of 4-aminosalicylic acid for their mitigating effect on experimental colitis in rats.

Abstract

Mutual amide prodrugs of 4-aminosalicylic acid with D-phenylalanine and L-tryptophan were synthesized for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. Stability studies in aqueous buffers (pH 1.2 and 7.4) showed that the synthesized prodrugs were stable in both the buffers over a period of 10 h. In rat fecal matter the release of 4-aminosalicylic acid from the prodrugs was in the range of 86-91% over a period of 20 h, with half-lives ranging between 343 and 412 min following first order kinetics. Targeting potential of the carrier system and the ameliorating effect of the amide conjugates were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model in rats. The prodrugs were assessed for their probable damaging effects on pancreas and liver with the help of histopathological analysis and for their ulcerogenic potential by Rainsford's cold stress method. They were found to have improved safety profile than sulfasalazine, oral 4- and 5-aminosalicylic acid with similar pharmacological spectrum and advantages of sulfasalazine.

• Authors: Suneela S Dhaneshwar, Mukta Chail, Mahavir Patil, Salma Naqvi, Gaurav Vadnerkar
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 44 Issue 1 Pg. 131-42 (Jan 2009) ISSN: 1768-3254 [Electronic] France
• PMID: 18472188 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Aminosalicylic Acids
• Prodrugs

Topics

• Aminosalicylic Acids (chemical synthesis, pharmacokinetics, pharmacology, toxicity)
• Animals
• Colitis (complications, drug therapy, prevention & control)
• Colon (metabolism)
• Drug Delivery Systems
• Drug Stability
• Drug-Related Side Effects and Adverse Reactions
• Liver (drug effects)
• Pancreas (drug effects)
• Prodrugs (chemical synthesis)
• Rats
• Ulcer (chemically induced)