TY - JOUR
T1 - Design, synthesis, and testing of a molecular truck for colonic delivery of 5-aminosalicylic acid
AU - Navath, Suryakiran
AU - Rao, Venkataramanarao
AU - Woodford, Rita Marie T.
AU - Midura-Kiela, Monica T.
AU - Ahad, Ali M.
AU - Alleti, Ramesh
AU - Kiela, Pawel R.
AU - Mash, Eugene A.
PY - 2012/9/13
Y1 - 2012/9/13
N2 - 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.
AB - 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.
KW - 5-aminosalicylic acid
KW - Inflammatory bowel disease
KW - pro-drug
UR - http://www.scopus.com/inward/record.url?scp=84866352814&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84866352814&partnerID=8YFLogxK
U2 - 10.1021/ml300086c
DO - 10.1021/ml300086c
M3 - Article
AN - SCOPUS:84866352814
VL - 3
SP - 710
EP - 714
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
SN - 1948-5875
IS - 9
ER -