Synthesis and Evaluation of Novel Tosylated Compounds as Selective Antibiofilm Agents against <i>Pseudomonas aeruginosa</i>

Antibiotic-resistant bacterial pathogens represent a critical global health challenge, largely due to their ability to form biofilms-structured microbial communities that protect bacteria from external threats and contribute to persistent, chronic infections. In this study, we evaluated the antibiofilm potential of tosylated molecules synthesized from propargyl alcohol and polyethylene glycol against Pseudomonas aeruginosa H103. Among the tested compounds, propargyl tosylate demonstrated potent antibiofilm activity by effectively disrupting both the formation and maintenance of biofilms. Notably, this activity was achieved without exhibiting direct antibacterial effects, indicating that the compound interferes with specific stages of biofilm development rather than bacterial viability. In contrast, Staphylococcus aureus biofilms remained unaffected, suggesting a potential selectivity of the compound toward Gram-negative bacteria. Structure-activity relationship analysis underlined the crucial role of the benzenesulfonate (tosyl) moiety in enhancing antibiofilm properties. These findings suggest that propargyl tosylate is a promising lead compound for the development of non-bactericidal agents specifically targeting P. aeruginosa biofilms, offering a novel approach in the fight against biofilm-associated infections.