Abstract

Gingivitis, the most common form of periodontal disease, affects nearly every individual at some stage of life. Chlorhexidine is widely used as the gold standard for its treatment; however, its potential cytotoxicity and irritant effects at higher concentrations necessitate the development of safer alternatives. This study investigates the in-silico docking potential of 2,4-di-tert-butylphenol (2,4-DTBP), a phenolic compound, against four key oral pathogens associated with gingivitis—Streptococcus mutans, Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum and Porphyromonas gingivalis. Two proteins involved in virulence and biofilm formation were selected from each species. Docking analysis with Autodock was done, which revealed, 2,4-DTBP displays binding affinities comparable to chlorhexidine. Furthermore, its absorption, distribution, metabolism, excretion and toxicity profile and drug-likeness were evaluated using Swiss Absorption, Distribution, Metabolism, Excretion, Protox, Predicting Small-Molecule Pharmacokinetic and Toxicity Properties Using Graph-Based Signatures and Molsoft tools, indicating acceptable pharmacokinetic properties with mild irritability. In addition, minimum inhibitory concentration evaluation demonstrated that both 2,4-DTBP and chlorhexidine exhibited measurable antibacterial activity, with 2,4- DTBP showing comparatively stronger inhibition, further supporting the in-silico findings. To improve therapeutic efficacy and minimize toxicity, the compound holds strong potential for delivery through advanced systems such as nanoparticles, nanoemulsions, liposomes, phytosomes and solid lipid nanoparticles, especially when encapsulated with biocompatible polymers. These platforms can enhance stability, targeted delivery and sustained release. Therefore, 2,4-DTBP can be considered a preliminary candidate for further development in gingivitis management, particularly within biocompatible, controlled-release delivery systems.

Key words: Gingivitis; 2,4-DTBP; Chlorhexidine; Autodock; ADMET