Regiospecific vs. non regiospecific click azide-alkyne polymerization: In vitro study of water-soluble antibacterial...

Novel linear cationic poly(amide aminotriazole)s (PATnD) with secondary amine groups in the backbone were obtained by using azide-alkyne 1,3-dipolar cycloaddition reactions: metal- and solvent-free (thermal conditions, PATTnD) or copper(I)-catalyzed (Sharpless conditions, PATCnD). PATnD were investigated in vitro against strains of E. coli, P. aeruginosa, S. aureus, and S. epidermidis. Hemolytic activity was tested using human red blood cells (hRBC), and very low or no hemolytic activity was observed. The cytotoxicity of PATnD polymers against Human Gingival Fibroblasts (HGnF) cells was concentration-dependent, and significant differences between PATT1D and PATC1D were observed. The ability of these polymers to induce resistance against both Gram-positive and Gram-negative bacteria was also assessed. Studied bacterial strains acquired resistance to catalytic polymers (PATCnD) in initial passages meanwhile resistance to thermal polymers (PATTnD) appears in later passages, being the increase of the minimum inhibitory concentration lower than in catalytic polymers. This result, together with the higher biocidal capacity of thermal polymers compared to catalytic ones, seems to suggest an influence of the regiospecificity of the polymers on their antibacterial characteristics. This study also demonstrates that PAT1D polymers, which do not appear to have strong hydrophobic residues, can exert significant antimicrobial activity against Gram-positive bacteria such as S. epidermidis. This pair of polymers, PATC1D and PATT1D, displays the greatest antimicrobial activity while not causing significant hemolysis along with the lowest susceptibility for resistance development of the polymers evaluated.