Sains Malaysiana 52(1)(2023): 199-210 http://doi.org/10.17576/jsm-2023-5201-16 In Vitro Antimicrobial, Antiglycolytic, and Antibioflm Activities of Synthetic 1,4-Naphthoquinone Derivatives against Cariogenic Bacteria (Aktiviti Antimikrob, Antiglikolitik dan Antibioflem In Vitro bagi Terbitan 1,4-Naftokuinon Sintetik terhadap Bakteria Kariogenik) PICHAYAPORN RATTI 1 , JUTHARAT MANUSCHAI 1 , JIRAPORN KARA 2,3 , LUELAK LOMLIM 2,3 & SUPAWADEE NAORUNGROJ 1,* 1 Department of Conservative Dentistry, Faculty of Dentistry, Prince of Songkla University, Hat Yai, Songkhla, Thailand 2 Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hat Yai, Songkhla, Thailand 3 Phytomedicine 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, 1 H-nuclear magnetic spectroscopy, 13 C- 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 efect on S. mutans bioflm 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 efect against S. mutans bioflm 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 bioflm; 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 1 H, spektroskopi magnet nuklear 13 C 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 bioflem 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