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. mutansand 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.

In vitro efficacy of synthetic lawsone derivative disinfectant solution on removing dual-species biofilms and effect on acrylic denture surface properties

“…It was anticipated that increasing the lipophilicity with this modification would enhance cell membrane permeation, thereby increasing antimicrobial effects on cells 32 . Compound 1 has antifungal and antibacterial properties 22 , 23 . Moreover, this NQs derivative exhibited potential antibiofilm activities against S. mutans and C. albicans single-species biofilms, according to previous reports 22 , 23 .…”

“…Compound 1 has antifungal and antibacterial properties 22 , 23 . Moreover, this NQs derivative exhibited potential antibiofilm activities against S. mutans and C. albicans single-species biofilms, according to previous reports 22 , 23 . The antimicrobial and antibiofilm activities of this compound may be attributable to its abilities to generate reactive oxygen species that can affect biomolecules such as DNA, protein and lipid, resulting in intracellular damage and apoptosis 21 .…”

“…Our previous study synthesized new lipophilic lawsone derivatives with enhanced antifungal and antibacterial activities for dental applications by changing the 2-hydroxyl group of lawsone to different alkynyloxy groups. Among the compounds in the series, 2-(prop-2-ynyloxy)naphthalene-1,4-dione (compound 1) demonstrated promising anti-candida, anti-cariogenic bacteria activities, and Streptococcus mutans ( S. mutans ) biofilm inhibition properties 22 , 23 . Compound 1 was efficiently synthesized via a simple alkylation reaction of lawsone with propargylbromide under basic condition and obtained as a yellow solid, with molecular weight of 212.20 Dalton, and melting point of 149–151 °C.…”