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

Eur J Med Chem. 2007 Jun;42(6):885-90. doi: 10.1016/j.ejmech.2006.11.017. Epub 2006 Dec 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

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

Substances

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