In Vitro Antimicrobial, Antiglycolytic, and Antibiofilm Activities of Synthetic 1,4-Naphthoquinone Derivatives against Cariogenic Bacteria

Abstract

This study investigated the potential anticaries properties of synthetic 1,4-naphthoquinone derivatives. Synthetic 1,4-naphthoquinone derivatives (2-4) were designed and synthesized by employing lawsone methyl ether (LME, 1), a plant-derived 1,4-naphthoquinone, as a lead compound. The synthetic compounds were characterized by infrared spectroscopy, 1H-nuclear magnetic spectroscopy, 13C- nuclear magnetic spectroscopy, and high-resolution mass spectrometry. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and growth curves were determined to assess their antibacterial effects against Streptococcus mutans, Lacticaseibacillus casei, and Actinomyces naeslundii. The pH drop assay was also performed on these three bacterial species. The effect on S. mutans biofilm formation was evaluated by crystal violet assay. From the microdilution assay, 2-(prop- 2-ynyloxy)naphthalene-1,4-dione (compound 2) showed potent antimicrobial activity against S. mutans and A. naeslundii (MIC of 1.56 and 3.125 μg/mL, respectively) in the same range as chlorhexidine (MIC of 1.95 and 1.95 μg/mL, respectively). The 1,4-naphthoquinone derivatives showed low antibacterial activity against L. casei. LME (compound 1) and 2-(prop-2-ynyloxy)naphthalene-1,4-dione (compound 2) inhibited pH reduction from S. mutans. The compounds at sub-MIC concentrations showed a potent inhibitory effect against S. mutans biofilm formation in a dose- and time-dependent manner. These results suggested that the synthetic 1,4-naphthoquinone derivatives are promising compounds that could be developed as a novel alternative or adjunctive anticaries therapies.