Studying the Inhibitory Effects of Some Chalcone Derivatives on Streptococcus mutans Sortase A to Prevent Dental Caries: An In Silico Approach

 Streptococcus mutans is one of the most important microorganisms in tooth decay. Sortase A (SrtA) of S. mutans is responsible for the attachment of bacteria to the host cell and biofilm formation. Therefore, it seems necessary to investigate the inhibitors of this enzyme to prevent dental caries. Chalcones are always of interest in the medical community due to their wide range of biological activities. Many studies have reported that chalcone can help prevent caries. The present study was conducted to identify potential SrtA inhibitors with the chalcone skeleton.

 The chalcone derivatives were obtained from the ZINC15, LEA3D, and PubChem databases, and then the selected compounds were optimized by HyperChem software. The affinity of these compounds to SrtA and total binding free energy (ΔGbind) were estimated by the AutoDock 4.0 program. Finally, drug-likeness screening and absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the best ligands were obtained using online servers.

 Compared to chalcone, four of the studied ligands, including compounds 2, 7, 8, and 9 demonstrated high affinity for binding to S. mutans SrtA, with suitable drug-likeness and ADMET properties. Ligand 9 interacted with the key residues in the active site by the most negative ΔGbind (-4.64 kcal/mol). The best conformation of this ligand had the most overlap with the chalcone.

 By complementary both in vitro and in vivo studies on the inhibitory effects of compounds 2, 7, 8, and 9, the present study can be useful in controlling tooth decay and dental diseases.