Evaluating Pharmacokinetics and Toxicity of Potential Therapeutics Against Enterococcus faecalis in Endodontic...

BACKGROUND This study explores pharmacokinetic profiles and safety parameters of candidate therapeutics targeting Enterococcus faecalis in endodontic infections. It examines absorption, distribution, metabolism, excretion characteristics, toxicity risk, and biocompatibility with periapical tissues. The objective is to identify clinically safe and efficacious compounds for endodontic application. MATERIAL AND METHODS Quantum chemical and molecular docking techniques evaluated the electronic structures of 5 bioactive compounds - 2-hydroxyethyl methacrylate, dimethyl adipate, dimethyl glutarate, dimethyl succinate, and ethylene glycol dimethyl acrylate - and their interactions with E. faecalis, a key endodontic infectious pathogen. These methods offer insights into binding affinities and drug behavior within the endodontic environment. Pharmacokinetic (ADME) studies were used to evaluate drug absorption and distribution, while toxicity assessments predicted potential adverse effects on organs, thereby ensuring safe and effective treatment of endodontic lesions. RESULTS We used Gaussian16 software to heighten the structures of 2-hydroxyethyl methacrylate, which enhances adhesion, along with dimethyl adipate, dimethyl glutarate, and dimethyl succinate, as compounds with probable endodontic applications. ADMET analyses were used to screen candidates for pharmacokinetic suitability and safety. Molecular docking was accomplished against the target protein E. faecalis, using AutoDock Vina and AutoDock Tools. Ethylene glycol dimethyl acrylate is the most promising candidate for endodontic applications owing to its binding affinity, metabolic stability, and efficient clearance. 2-Hydroxyethyl methacrylate has promising electrostatic potential and pharmacokinetics, while dimethyl succinate has low binding affinity and carcinogenicity concerns. CONCLUSIONS Results suggests that 2-hydroxyethyl methacrylate, dimethyl adipate, dimethyl glutarate, dimethyl succinate, and ethylene glycol dimethyl acrylate bind to E. faecalis, a key pathogen in endodontic infections.