Identification of Potential Glucosyltransferase Inhibitors from Cinnamic Acid Derivatives Using Molecular Docking Analysis: A Bioinformatics Study

Abstract

Background: Dental caries is one of the most common oral chronic diseases. Streptococcus mutans is the main pathogenic bacteria playing a role in degrading the mineral texture of the teeth. Glucosyltransferase (GTFase) of S. mutans is responsible for producing glucan, which is the main exopolysaccharide found in the cariogenic biofilms. Further, previous studies have reported that cinnamic acid diminished biofilm formation of S. mutans. Therefore, we hypothesized that cinnamic acid and its derivatives might act as GTFase inhibitors. Methods: The binding affinity of a total of 12 plant-based compounds including cinnamic acid and its 11 derivatives to the GTFase active site were examined by utilizing the AutoDock tool. The possible interactions between top-ranked cinnamic acid derivatives and the residues within the GTFase catalytic site were also taken into consideration. Results: Five of the cinnamic acid derivatives including rosmarinic acid (RA), cynarine, chlorogenic acid (CGA), caffeic acid 3-glucoside, and N-p-coumaroyltyramine demonstrated inhibitory effects on GTFase at nanomolar concentration. Stabilizing interactions such as π–π stack pairing and pi-charge interactions were detected between top-ranked GTFase inhibitors and residues within the enzyme active site. Conclusions: The present study suggests that RA, cynarine, CGA, caffeic acid 3-glucoside, and N-p-coumaroyltyramine might have protective effects on dental caries, and therefore, may be considered as anti-tooth caries compounds.