RESUMO
A library of 29 small 1,4-substituted 1,2,3-triazoles was prepared for studies of antimicrobial activity. The pharmacophore model investigated with these substrates was based on small peptidomimetics of antimicrobial peptides and antimicrobials isolated from marine organisms from sub-arctic regions. Using methyl 1,2,3-triazole-carboxylates and 1,2,3-triazole methyl ketones prepared through "click" chemistry we were able to synthesize the different cationic amphiphiles through three steps or less. Several structural modifications to the lipopohilic side and hydrophilic sides of the amphiphiles were investigated and compared with regards to antimicrobial activity and cytotoxicity in particular. The most promising amphiphile 10f displayed minimum inhibitory concentrations (MICs) between 4-16µg/mL against Gram-positive Enterococcus faecalis, Staphylococcus aureus, Streptococcus agalacticae, and Gram-negative Escherichia coli and Pseudomonas aeruginosa. The decent level of antimicrobial activity and biofilm inhibition, short synthesis, and accessible reagents, makes this type of amphiphilic mimics interesting leads for further development.
Assuntos
Alcinos/química , Antibacterianos/farmacologia , Butiratos/química , Propionatos/química , Tensoativos/farmacologia , Triazóis/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Relação Dose-Resposta a Droga , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Peptidomiméticos , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus/efeitos dos fármacos , Relação Estrutura-Atividade , Tensoativos/síntese química , Tensoativos/química , Triazóis/síntese química , Triazóis/químicaRESUMO
A library of 28 small cationic 1,4-substituted 1,2,3-triazoles was prepared for studies of antimicrobial activity. The structures addressed the pharmacophore model of small antimicrobial peptides and an amphipathic motif found in marine antimicrobials. Eight compounds showed promising antimicrobial activity, of which the most potent compound 10b displayed minimum inhibitory concentrations of 4-8µg/mL against Streptococcus agalacticae, Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis. The simple syntheses and low degree of functionalization make these 1,4-substituted 1,2,3-triazoles interesting for further optimizations.