Impact of Structural Modifications on the In Vitro Antibacterial Activity of Methylenedioxy Lignan Derivatives against Oral Pathogens: Synthesis and Molecular Docking Studies

The present study investigates the impact of systematic structural modifications within the methylenedioxy-lignan scaffold on their in vitro antibacterial activity against selected oral pathogens, integrating experimental assays with molecular docking analyses. The synthetic methodology commenced with reactions involving piperonal, yielding the lactone 4-(3′,4′-methylenedioxyphenyl)-4,5-dihydro-2(3 H)-furanone ( 5 ). Further reaction of piperonal with compound 5 yielded 7-hydroxyhinokinin ( 6 ), which served as a key intermediate for the synthesis of 10 related derivatives ( 7–16 ). The antibacterial activity of these compounds was assessed against Enterococcus faecalis , Streptococcus salivarius , Streptococcus sanguinis , Lactobacillus casei , Streptococcus mutans , Streptococcus sobrinus , and Streptococcus mitis . Derivatives 9–13 exhibited no detectable activity within the tested concentration range. Compound 15 demonstrated the lowest MIC value against L. casei (80 µg/mL), while compound 14 exhibited the lowest MIC value against S. sanguinis (100 µg/mL). Variations in antibacterial activity among these compounds appear to be associated with the presence or absence of a hydroxyl group, which may modulate the response depending on the microorganism. Compounds 7 and 8 displayed measurable MIC values against all tested microorganisms except E. faecalis , whereas compound 16 showed selective activity against S. sobrinus (MIC = 400 µg/mL). Compound 6 exhibited an MIC of 300 µg/mL against S. mutans . Molecular docking analysis corroborated the experimental findings, indicating that hydrogen bonding and hydrophobic interactions contribute to ligand–target binding. These results demonstrate that structural modifications influence the antibacterial activity of the methylenedioxy-lactone-lignan scaffold and underscore its potential for investigating structure–activity relationships.