Synthesis and in vitro evaluation of N-nicotinoylglycyl-2-(5-fluorouracil-1-yl)-D,L-glycine as a colon-specific prodrug of 5-fluorouracil.

N-Nicotinoylglycyl-2-(5-fluorouracil-1-yl)-D,L-glycine (NGFG) was synthesized as a colon-specific prodrug of 5-fluorouracil (5-FU) expecting that hydrolysis of nicotinoyl and glycyl moieties by microbial enzymes in the colon will give 2-(5-fluorouracil-1-yl)-D,L-glycine, which releases 5-FU spontaneously. To in vitro-evaluate colon targetability of NGFG, apparent partition coefficient and chemical/biochemical stability of NGFG in the contents or/and tissue of the various segments of the gastrointestinal tract were determined. Low partition coefficient and stability of NGFG in the upper intestinal condition suggested its delivery to the colon in intact form after oral administration.

Evaluation of 5-aminosalicyltaurine as a colon-specific prodrug of 5-aminosalicylic acid for treatment of experimental colitis.

We previously reported that 5-aminosalicyltaurine (taurine-conjugated 5-ASA, 5-ASA-Tau) showed a potential as a colon-specific prodrug of 5-aminosalicylic acid (5-ASA) by in vitro evaluation. In this report, we in vivo-evaluated 5-ASA-Tau as a colon-specific prodrug for treatment of experimental colitis. Taurine conjugation of 5-ASA greatly reduced absorption of 5-ASA from the intestine.

A molecular mechanism for the anti-inflammatory effect of taurine-conjugated 5-aminosalicylic acid in inflamed colon.

In previous reports, a novel colon-specific prodrug, 5-aminosalicyltaurine (5-ASA-Tau) administered orally, is successfully delivered to and liberates 5-aminosalicylic acid (5-ASA) and taurine in the inflamed large intestine of rats. Furthermore, the prodrug ameliorates the 2,4,6-trinitrobenzene-sulfonic acid-induced colitis, and taurine acts not only as a carrier but also as an active therapeutic agent. In this study, we investigated the anti-inflammatory properties of the prodrug at a molecular level.

Metabolic and pharmacological properties of rutin, a dietary quercetin glycoside, for treatment of inflammatory bowel disease.

Purpose: Orally administered rutin reportedly ameliorates 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis of rats. We investigated the metabolic and pharmacological properties of rutin underlying the rutin-mediated amelioration of the rat colitis.

Methods: Apparent partition coefficients of rutin and its aglycone quercetin were compared.