We hypothesized that the formation of biofilms contributes to the onset of inflammatory bowel disease and, thus, attempted to develop biofilm inhibitors as potential treatment options. We identified a compound (1) with biofilm inhibitory activity in vitro; however, its rate of delivery to the target site, the colon, was low due to its high lipophilicity and low solubility. To improve the colon delivery rate, we considered a prodrug approach through glucuronidation. The glucuronide (3) showed a significant improvement in the in vivo colon delivery rate by avoiding absorption in the small intestine through a reduction in membrane permeability. Furthermore, in a murine disease model featuring dextran sulfate sodium-induced colitis, we confirmed that compound 3 increased the length of the colon approximately three times more than compound 1 did on a dosage basis.
Shimizu et al. (Mon,) studied this question.