Abstract
OBJECTIVE: Postoperative infection is one of the most common complications in dental procedures. During local anesthesia in dental treatments, the risk of postoperative infections increases if the oral mucosa is infected, the anesthesia injection site is inadequately disinfected, or the injection needle and anesthetic drugs are contaminated. Thus, developing new oral local anesthetics that offer superior anesthesia, enhanced safety, and antimicrobial properties could greatly enhance their clinical value. METHODS: The anesthetic effects and antibacterial properties of articaine derivatives were screened using membrane chromatography techniques, animal experiments, and cellular molecular assays. Safety assessments were conducted on the selected target compounds. Additionally, the antibacterial mechanisms of the compounds were investigated through molecular dynamics simulations and cryo-electron microscopy. RESULTS: Through the screening of articaine derivatives, a novel local anesthetic, AT-15, was identified, which combines effective anesthetic properties with antibacterial activity. This compound exhibits strong pharmacological activity and high safety. Its antibacterial effect is believed to result from the disruption of bacterial cell membranes and the inhibition of topoisomerase, an enzyme essential for bacterial DNA synthesis. CONCLUSION: AT-15 discovered in this study is a promising candidate for further development in clinical settings.