Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Physical Sciences, Biochemistry & Molecular Biology, Chemistry, Medicinal, Chemistry, Organic, Pharmacology & Pharmacy, Chemistry, Biofilm inhibition, Dimers, 2-Aminoimidazoles, Microwave assisted synthesis, PSEUDOMONAS-AERUGINOSA BIOFILMS, SURFACE ACOUSTIC-WAVES, SALMONELLA-TYPHIMURIUM, ONE-POT, INFECTIONS, INHIBITORS, 2-AMINOIMIDAZOLES, TOXICITY, PROMOTER, ANALOGS, Anti-Bacterial Agents, Biofilms, Biological Products, Dimerization, Dose-Response Relationship, Drug, Escherichia coli, Imidazoles, Microbial Sensitivity Tests, Microwaves, Molecular Structure, Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus, Structure-Activity Relationship, 0304 Medicinal and Biomolecular Chemistry, 0305 Organic Chemistry, 1115 Pharmacology and Pharmaceutical Sciences, Medicinal & Biomolecular Chemistry, 3101 Biochemistry and cell biology, 3404 Medicinal and biomolecular chemistry, 3405 Organic chemistry

Abstract:

The increased tolerance of biofilms against disinfectants and antibiotics has stimulated research into new methods of biofilm prevention and eradication. In our previous work, we have identified the 5-aryl-2-aminoimidazole core as a scaffold that demonstrates preventive activity against biofilm formation of a broad range of bacterial and fungal species. Inspired by the dimeric nature of natural 2-aminoimidazoles of the oroidin family, we investigated the potential of dimers of our decorated 5-aryl-2-aminoimidazoles as biofilm inhibitors. A synthetic approach towards 2-aminoimidazole dimers linked by an alkyl chain was developed and a total of 48 dimers were synthesized. The linkers were introduced at two different positions, the N1-position or the N2-position, and the linker length and the substitution of the 5-phenyl ring (H, F, Cl, Br) were varied. Although, no clear correlation between linker length and biofilm inhibition was observed, a strong increase in anti-biofilm activity for almost all N1,N1'-linked dimers was obtained, compared to the respective monomers against Salmonella Typhimurium, Escherichia coli and Staphylococcus aureus. The N2,N2'-linked dimers, having a H- or F-substitution, were also found to show a strong increase in anti-biofilm activity compared to the respective monomers against these three bacterial species and against Pseudomonas aeruginosa. In addition, the obtained growth measurements suggest a broad concentration range with specific biofilm inhibition and no effect on the planktonic growth against Salmonella Typhimurium and Pseudomonas aeruginosa.