In Silico Identification and ADME/Toxicity Prediction of Phytochemical Inhibitors Targeting Glucosyltransferases of Streptococcus mutans for Anti-Biofilm Applications

Abstract Dental caries remains a major global health concern, with Streptococcus mutans recognized as a key cariogenic pathogen due to its capacity to form resilient biofilms. Central to this process are the glucosyltransferases (GtfB, GtfC, and GtfD), which synthesize extracellular glucans that promote bacterial adhesion and biofilm stability. Targeting these enzymes represents a promising strategy for anti-caries therapy. In this study, we employed molecular docking and in silico pharmacokinetic profiling to evaluate the inhibitory potential of 21 phytochemicals against S. mutans glucosyltransferases. Docking analysis revealed that several compounds, including sanguinarine, rutin, quercetin, and chelerythrine, exhibited strong binding affinities across all three GTFs (− 7.4 to − 9.5 kcal/mol), often surpassing the binding affinities of known inhibitors. Ligand–protein interaction analysis identified recurrent hotspots such as Gln592 in GtfC and Gln347 in GtfD, underscoring conserved binding pockets. ADME and toxicity predictions further suggested that most top-ranking compounds possessed favorable pharmacokinetic properties with acceptable safety profiles, highlighting their potential as lead molecules. Overall, this integrated computational study identifies multiple plant-derived inhibitors with promising activity against S. mutans glucosyltransferases, supporting their further evaluation as natural anti-biofilm and anti-caries agents.