Chalcone derivatives against biofilm production of Streptococcus mutans by glucosyltransferase C inhibition.

Dental caries remain an unresolved public health issue. Streptococcus mutans, a principal microorganism in the mouth, is closely associated with the onset and progression of dental caries. S. mutans adheres to tooth surfaces and synthesizes extracellular polysaccharides via the enzyme glucosyltransferase (Gtf), utilizing sucrose and forming biofilms. GtfC is linked to soluble and insoluble glucan synthesis, a significant factor in the adhesion of S. mutans to tooth surfaces and bacterial cell aggregation within biofilms. Chalcones, primary precursors for flavonoid and isoflavonoid biosynthesis, have demonstrated notable therapeutic efficacy in treating various diseases, including anti-inflammatory, antibacterial, and anticancer effects. This study aims to evaluate the inhibitory effects of six chalcone derivatives on GtfC, the prevention of biofilm formation by S. mutans, and the assessment of the cytotoxicity of these derivatives. To predict interactions between chalcone derivatives (5a, 5b, 5d, 5h, NME2, and BA) and GtfC, molecular docking was employed. The effectiveness of chalcone derivatives in inhibiting S. mutans biofilm formation and evaluating the potential of the compounds to destroy biofilms was assessed using a colorimetric method, with dye absorbance measured by an ELISA reader. The same method was applied for cytotoxicity assessment. All chalcone derivatives inhibited the growth of S. mutans, S. sanguinis, and S. salivarius, exhibiting antibiofilm properties against S. mutans. Compounds 5a, 5b, 5d, and NME2 successfully eradicated the S. mutans biofilm. All compounds demonstrated low cytotoxicity on HepG2 cells. The results indicate that compound 5a exhibited the strongest effect among the six chalcone derivatives, showing effectiveness at lower concentrations in all assays, including MBIC and MBEC tests.