Comparative evaluation of a novel piperazine-chalcone hybrid and calcium hydroxide formulations against root canal...

Root canal infections, particularly those involving Enterococcus faecalis and Candida albicans, continue to pose significant challenges in endodontic therapy due to both their inherent resistance to conventional agents. This study aimed to evaluate the antimicrobial efficacy of a newly synthesized piperazine-chalcone hybrid compound, both individually and in various formulations with calcium hydroxide, against these clinically relevant pathogens. The antimicrobial activities were assessed using the disk diffusion method over 24 and 48 h, whereas in silico analyses were conducted to further investigate the compound's molecular interactions, pharmacokinetics, and toxicity potential. Results demonstrated that the piperazine-chalcone hybrid exhibited strong antimicrobial activity against both pathogens, with inhibition zone diameters ranging from approximately 26-32 mm against E. faecalis and 18-28 mm against C. albicans, exceeding those observed for calcium hydroxide and standard antimicrobial controls. Molecular docking analysis revealed favorable binding interactions of the hybrid compound with d-alanine:d-alanine ligase, with a docking score of -8.6 kcal/mol. In silico toxicological assessment predicted a favorable safety profile, with an LD₅₀ value >5000 mg/kg and no major toxicity alerts. These findings suggest that the piperazine-chalcone hybrid holds promise as a safe and effective candidate for enhanced endodontic disinfection.