Synthesis, kinetic studies and pharmacological evaluation of mutual azo prodrug of 5-aminosalicylic acid for colon-specific drug delivery in inflammatory bowel disease.

Abstract

Mutual azo prodrug of 5-aminosalicylic acid with l-tyrosine was synthesized by coupling l-tyrosine with salicylic acid, for targeted drug delivery to the inflamed gut tissue in inflammatory bowel disease. The structure was confirmed by elemental analysis, IR and NMR spectroscopy. In vitro kinetic studies in rat fecal matter showed 87.18% release of 5-aminosalicylic acid with a half-life of 140.28min, following first order kinetics. Therapeutic efficacy of the carrier system and the mitigating effect of the azo conjugate were evaluated in trinitrobenzenesulfonic acid-induced experimental colitis model. Myeloperoxidase activity was determined by the method of Krawisz et al. The synthesized prodrug was found to produce comparable mitigating effect as that of sulfasalazine on colitis in rats.

• Authors: Suneela S Dhaneshwar, Mini Kandpal, Gaurav Vadnerkar, Badal Rathi, S S Kadam
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 42 Issue 6 Pg. 885-90 (Jun 2007) ISSN: 0223-5234 [Print] France
• PMID: 17258353 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)

Chemical References

• Aminosalicylic Acids
• Anti-Inflammatory Agents, Non-Steroidal
• Prodrugs

Topics

• Aminosalicylic Acids (administration & dosage, chemical synthesis, pharmacokinetics, pharmacology)
• Animals
• Anti-Inflammatory Agents, Non-Steroidal (administration & dosage, chemical synthesis, pharmacokinetics, pharmacology)
• Colitis (chemically induced, drug therapy)
• Colon (metabolism)
• Female
• Male
• Molecular Structure
• Organ Specificity
• Prodrugs (administration & dosage, chemical synthesis, pharmacokinetics, pharmacology)
• Rats
• Rats, Wistar