title: Design, Synthesis, and Testing of a Molecular Truck for Colonic Delivery of 5-Aminosalicylic Acid.
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 hours following administration of the pro-drug. Thus, a new, orally administered pro-drug form of 5-aminosalicylic acid has been developed and successfully demonstrated.
authors.affiliation: Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721.
authors.forename: Suryakiran
authors.initials: S
authors.lastname: Navath
authors.forename: Venkataramanarao
authors.initials: V
authors.lastname: Rao
authors.forename: Rita-Marie T
authors.initials: RM
authors.lastname: Woodford
authors.forename: Monica T
authors.initials: MT
authors.lastname: Midura-Kiela
authors.forename: Ali M
authors.initials: AM
authors.lastname: Ahad
authors.forename: Ramesh
authors.initials: R
authors.lastname: Alleti
authors.forename: Pawel R
authors.initials: PR
authors.lastname: Kiela
authors.forename: Eugene A
authors.initials: EA
authors.lastname: Mash