Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of .

We designed and synthesized analogues of a previously identified biofilm inhibitor to improve solubility, retain inhibitory activities, and to facilitate encapsulation into pH-responsive hydrogel microparticles. The optimized lead compound showed improved solubility of 120.09 μg/mL, inhibited biofilm with an IC value of 6.42 μM, and did not affect the growth of oral commensal species up to a 15-fold higher concentration. The cocrystal structure of with GtfB catalytic domain determined at 2.35 Å resolution revealed its active site interactions. The ability of to inhibit Gtfs and to reduce glucan production has been demonstrated. The hydrogel-encapsulated biofilm inhibitor (), generated by encapsulating in hydrogel, selectively inhibited biofilms like . Treatment of -infected rats with or resulted in a significant reduction in buccal, sulcal, and proximal dental caries compared to untreated, infected rats.