Antimicrobial and Antibiofilm Activities of Synthetic Lawsone Derivatives Containing N-Substituted 1,2,3-Triazole Against Dental Caries Pathogens

Abstract

Objective: Presently, one of the most common oral diseases is dental caries, which is a biofilm-mediated disease. Lawsone methyl ether (LME) has shown promising antibacterial activity due to its 1,4-napthoquinone structure. Recently, a 1,2,3-triazole scaffold has been used in the structural modification of potential antimicrobial agents. To develop novel anticaries agents, the structure modification of 1,4-napthoquinone with N-substituted 1,2,3-triazole, therefore, may be a candidate. Material and Methods: LME was used as a lead compound, and three new lawsone derivatives were prepared by two-step reactions. Their antimicrobial effects against three dental caries pathogens; including S. mutans, L. casei, and A. naeslundii were investigated, using the microdilution technique (0.78-100 μg/mL). A growth curve assay was performed to assess the effects of compounds on the growth kinetics of bacteria. Moreover, the effect of synthetic lawsone derivatives on the biofilm formation of S. mutans was also evaluated by crystal violet assay. Results: Overall, S. mutans was most sensitive to lawsone derivatives (minimum inhibitory concentration (MIC)=1.56- 50 μg/mL), followed by A. naeslundii and L. casei: corresponding to their growth curves. Lawsone derivatives, at the concentration of 1/2 MIC and 1/4 MIC, inhibited 12-hour S. mutans biofilm formation by 86.0-98.0%. The inhibitory effect decreased with decreasing concentrations and increasing incubation times. Conclusion: Synthetic lawsone derivatives have an inhibitory effect on the growth of three tested cariogenic bacteria, and the biofilm formation of S. mutans. The compounds exhibited anti-cariogenic bacterial strains and satisfying antibiofilm formation effects on S. mutans.