Sains Malaysiana 52(1)(2023): 199-210

http://doi.org/10.17576/jsm-2023-5201-16

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

(Aktiviti Antimikrob, Antiglikolitik dan Antibiofilem In Vitro bagi Terbitan 1,4-Naftokuinon Sintetik terhadap Bakteria Kariogenik)

PICHAYAPORN RATTI¹, JUTHARAT MANUSCHAI¹, JIRAPORN KARA^2,3, LUELAK LOMLIM^2,3 & SUPAWADEE NAORUNGROJ^1,*

¹Department of Conservative Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Songkhla, Thailand

²Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand

³Phytomedicine and Pharmaceutical Biotechnology Excellent Center (PPBEC), Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand

Received: 11 June 2022/Accepted: 29 September 2022

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.

Keywords: Acid production; antibacterial activity; dental biofilm; dental caries; 1,4-naphthoquinone

Abstrak

Penyelidikan ini mengkaji potensi sifat antikaries bagi terbitan 1,4-naftokuinon sintetik. Terbitan 1,4-naftokuinon sintetik (2-4) telah direka dan disintesis dengan menggunakan lawsone metil eter (LME, 1), 1,4-naftokuinon yang berasal daripada tumbuhan, sebagai sebatian plumbum. Sebatian sintetik telah dicirikan oleh spektroskopi inframerah, spektroskopi magnet nuklear ¹H, spektroskopi magnet nuklear ¹³C dan spektrometri jisim resolusi tinggi. Kepekatan perencatan minimum (MIC), kepekatan bakteria minimum (MBC) dan lengkung pertumbuhan ditentukan untuk menilai kesan antibakteria mereka terhadap Streptococcus mutans, Lacticaseibacillus casei dan Actinomyces naeslundii. Ujian penurunan pH juga dilakukan ke atas ketiga-tiga spesies bakteria ini. Kesan ke atas pembentukan biofilem S. mutans dinilai dengan ujian kristal violet. Daripada ujian pencairan mikro, 2-(prop-2-yniloksi)naftalena-1,4-dion (sebatian 2) menunjukkan aktiviti antimikrob yang kuat terhadap S. mutans dan A. naeslundii (masing-masing MIC 1.56 dan 3.125 µg/mL) dalam julat yang sama seperti klorheksidin (masing-masing MIC 1.95 dan 1.95 µg/mL). Terbitan 1,4-naftokuinon menunjukkan aktiviti antibakteria yang rendah terhadap L. casei. LME (sebatian 1) dan 2-(prop-2-yniloksi)naftalena-1,4-dione (sebatian 2) menghalang pengurangan pH daripada S. mutans. Sebatian pada kepekatan sub-MIC menunjukkan kesan perencatan yang kuat terhadap pembentukan biofilem S. mutans dalam cara yang bergantung kepada dos dan masa. Keputusan ini mencadangkan bahawa terbitan 1,4-naftokuinon sintetik adalah sebatian yang menyakinkan dan boleh dibangunkan sebagai alternatif baru atau terapi antikaries tambahan.

Kata kunci: Aktiviti antibakteria; biofilem gigi; karies gigi; penghasilan asid; 1,4-naftokuinon

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^*Corresponding author; email: supawadee.n@psu.ac.th