Tackling Antibiotic Resistance: Influence of Aliphatic Branches on Broad-Spectrum Antibacterial Polytriazoles against ESKAPE Group Pathogens

• Published in: Pharmaceutics Vol. 14; no. 11; p. 2518
• Main Authors: Rangel-Núñez, Cristian, Molina-Pinilla, Inmaculada, Ramírez-Trujillo, Cristina, Suárez-Cruz, Adrián, Martínez, Samuel Bernal, Bueno-Martínez, Manuel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-11-2022; MDPI
• Subjects: antibacterial polymer; antibiotic resistance; Antibiotics; Antimicrobial agents; Bacteria; cationic polymer; Chemistry; Chromatography; click polymerization; Control; Cross infection; Dosage and administration; Drug discovery; Drug resistance in microorganisms; ESKAPE; Identification and classification; Methods; Nosocomial infections; Pathogenic microorganisms; Pathogens; Penicillin; Polymers; Prevention; Risk factors; Solvents; Staphylococcus infections; Spain; United States > US; ESKAPE; cationic polymer; click polymerization; antibacterial polymer; antibiotic resistance
• ISSN: 1999-4923; 1999-4923
• DOI: 10.3390/pharmaceutics14112518

One of the most important threats to public health is the appearance of multidrug-resistant pathogenic bacteria, since they are the cause of a high number of deaths worldwide. Consequently, the preparation of new effective antibacterial agents that do not generate antimicrobial resistance is urgently required. We report on the synthesis of new linear cationic antibacterial polytriazoles that could be a potential source of new antibacterial compounds. These polymers were prepared by thermal- or copper-catalyzed click reactions of azide and alkyne functions. The antibacterial activity of these materials can be modulated by varying the size or nature of their side chains, as this alters the hydrophilic/hydrophobic balance. Antibacterial activity was tested against pathogens of the ESKAPE group. The P3TD polymer, which has butylated side chains, was found to have the highest bactericidal activity. The toxicity of selected polytriazoles was investigated using human red blood cells and a human gingival fibroblast cell line. The propensity of prepared polytriazoles to induce resistance in certain bacteria was studied. Some of them were found to not produce resistance in methicillin-resistant
or
. The interaction of these polytriazoles with the
membrane produces both depolarization and disruption of the membrane.