Mono- and Bis-Cationic Synthetic Polymers with Antibacterial, Antibiofilm, and Anticancer Activities

Abstract A series of polymers containing ammonium cations alone or together with sulfonium cations were synthesized and evaluated for antibacterial, antibiofilm, and anticancer activities. The polymers showed potent activity against Bacillus subtilis, Escherichia coli K-12, and methicillin-resistant Staphylococcus aureus (MRSA). Bis-cationic polymer 2c, bearing hexyl substituents, exhibited the strongest antibacterial effect, with an MIC of 1 μg/mL against B. subtilis, and showed bactericidal activity against Gram-negative strains. Mechanistic studies indicated membrane permeabilization and structural disruption as the primary antibacterial pathways. Several polymers also displayed strong antibiofilm activity and excellent hemocompatibility. Bis-cationic polymers 2e and 4a showed the highest anticancer activity, with IC50 values of 8.45 and 9.37 μg/mL against MDA-MB-231 and HCT116 cells, respectively. Their anticancer effects involved mitochondria-mediated apoptosis, enhanced mitochondrial ROS generation, and membrane depolarization, highlighting these polymers as promising multifunctional biomedical materials.