Design, synthesis, and testing of a molecular truck for colonic delivery of 5-aminosalicylic acid

Suryakiran Navath, Venkataramanarao Rao, Rita Marie T. Woodford, Monica T. Midura-Kiela, Ali M. Ahad, Ramesh Alleti, Pawel R. Kiela, Eugene A. Mash

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

A molecular scaffold bearing eight terminal alkyne groups was synthesized from sucrose. Eight copies of an azide-terminated, azo-linked precursor to 5-aminosalicylic acid were attached to the scaffold via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting compound was evaluated in a DSS model of colitis in BALB/c mice against sulfasalazine as a control. Two independent studies verified that the novel pro-drug, administered in a dose calculated to result in an equimolar 5-ASA yield, outperformed sulfasalazine in terms of protection from mucosal inflammation and T cell activation. A separate study established that 5-ASA appeared in feces produced 24-48 h following administration of the pro-drug. Thus, a new, orally administered pro-drug form of 5-aminosalicylic acid has been developed and successfully demonstrated.

Original languageEnglish (US)
Pages (from-to)710-714
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume3
Issue number9
DOIs
StatePublished - Sep 13 2012

Keywords

  • 5-aminosalicylic acid
  • Inflammatory bowel disease
  • pro-drug

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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