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Dental caries occur as a result of disequilibrium between acid producing pathogenic bacteria and alkali generating commensal bacteria within a dental biofilm (dental plaque).  Streptococcus mutans  has been reported as a primary cariogenic pathogen associated with dental caries. Emergence of multidrug resistant as well as fluoride resistant strains of  S. mutans  due to over use of various antibiotics are a rising problem and prompted the researchers worldwide to search for alternative therapies. In this perspective, the present study was aimed to screen selective inhibitors against ComA, a bacteriocin associated ABC transporter, involved in the quorum sensing of  S. mutans . In light of our present  in silico  findings, 1,3-disubstituted urea derivatives which had better affinity to ComA were chemically synthesized in the present study for  in vitro  evaluation of  S. mutans  biofilm inhibition. The results revealed that 1,3-disubstituted urea derivatives showed good biofilm inhibition. In addition, synthesized compounds exhibited potent synergy with a very low concentration of fluoride (31.25–62.5 ppm) in inhibiting the biofilm formation of  S. mutans  without affecting the bacterial growth. Further, the results were supported by confocal laser scanning microscopy. On the whole, from our experimental results we conclude that the combinatorial application of fluoride and disubstituted ureas has a potential synergistic effect which has a promising approach in combating multidrug resistant and fluoride resistant  S. mutans  in dental caries management.

Combinatorial Effects of Aromatic 1,3-Disubstituted Ureas and Fluoride on In vitro Inhibition of Streptococcus mutans Biofilm Formation