Affiliation:
1. Faculty of Chemistry Warsaw University of Technology Noakowskiego 3 Warsaw 00–664 Poland
2. School of Pharmacy University of Nottingham Boots Science Building, University Park Nottingham NG7 2RD UK
3. Laboratory of White Biotechnology Institute of Biochemistry and Biophysics Polish Academy of Sciences Pawińskiego 5a Warsaw 02–106 Poland
4. Centre for Advanced Materials and Technology (CEZAMAT) Warsaw University of Technology Poleczki 19 Warsaw 02–822 Poland
Abstract
AbstractNumerous synthetic polymers, imitating natural antimicrobial peptides, have demonstrated potent antimicrobial activity, positioning them as potential candidates for new antimicrobial drugs. However, the high activity of these molecules often comes at the cost of elevated toxicity against eukaryotic organisms. In this study, a series of cationic ionenes with varying molecular weights to assess the influence of polymer chain length on ionene activity is investigated. To enhance polymer antimicrobial activity and limit toxicity a PEG side chain is introduced into the repeating unit. The resulting molecules consistently exhibited high activity against three model organisms: E. coli, S. aureus and C. albicans. The incorporation of side PEG chain improves antifungal properties and biocompatibility, regardless of molecular weight. The most important finding of this work is that the reduction of polymer molecular mass led to increased antifungal activity and reduced cytotoxicity against HMF and MRC‐5 cell lines simultaneously. As a result, the best‐performing molecules reported herein displayed minimal inhibitory concentrations (MIC) as low as 2 and 0.0625 µg mL1 for C. albicans and C. tropicalis respectively, demonstrating exceptional selectivity. It is plausible that some of described herein molecules can serve as potential lead candidates for new antifungal drugs.