Excessive and incorrect use of antimicrobial agents leads to increasing bacterial resistance to antibiotics. The main reason for this are bacterial biofilms, which provide bacteria with physical protection and facilitate the development of various resistance mechanisms. Instead of disinfectants and antiseptics, which are often ineffective, we could develop surface biocidal coatings that would prevent the formation of biofilms or accelerate their dispersal, and would also have a destructive effect on bacteria. With such a dual action, the antimicrobial action would be much more effective, and the development of bacterial resistance would be slower.
For this purpose, we developed the synthesis procedures of various reagents for the formation of surface biocidal coatings. One part of this coating would be a silylating reagent that would be bound to glass, and the other part of the coating would be the biocidal part of the compound. Biocidal molecules would be cationic biocides and new bacterial topoisomerase inhibitors (NBTIs). The reagents would also contain an azide or alkyne group for the purpose of coating formation.
Cationic biocides would disperse the bacterial biofilm through interactions with the negative molecules of the biofilm and the cytoplasmic membrane of the bacteria. Upon contact with bacteria, there would be a loss of integrity of the cytoplasmic membrane, increased permeability, leakage of important cytoplasmic components into the environment and consequent bacterial death. NBTIs, on the other hand, inhibit the main task of bacterial topoisomerases type II, which is to reduce topological stress on DNA. This prevents the proper replication and transcription of the DNA, which leads to the death of the bacterium.
We have successfully synthesized three silylating reagents, one cationic biocide and two compounds with azide groups, which are ready for attachment of different biocidal molecules. The synthesis of NBTI was in too low a yield to make it worthwhile to proceed with this compound, and the synthesis of two compounds with azide groups was unsuccessful due to the formation of side products. In the future, the synthesized reagents would be combined with click reactions. These are fast and conditionally undemanding reactions that have high yields, and the isolation of the products is simple, so it would be possible to form different combinations between alkynes and azides in a relatively short time and test the biocidal activity of the coatings with biological tests.
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