Structure–activity relationship study of cationic carbosilane dendritic systems as antibacterial agents

Abstract

This work focuses on the antibacterial activity against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli and the hemolytic properties of two types of ammonium cationic carbosilane systems: dendrimers and dendrons. The effects of: (i) the generation, (ii) the type of peripheral groups near the cationic charges (a SiMe₂ moiety or a S atom depending on the synthetic procedure, hydrosilylation or thiol–ene addition, respectively), (iii) the core of dendrimers (polyphenoxo vs. Si atom) and (iv) the focal point of dendrons (–N₃, –NH₂, –OH) have been assessed. The structure–activity relationship analysis indicates the importance of an adequate balance between the hydrophilic and lipophilic fragments of these molecules to reach the best antibacterial activity. Regarding hemolysis, lowest toxicity values were registered for dendritic systems with a sulfur atom close to the surface and, in the particular case of dendrons, for those with a hydroxyl focal point. One dendrimer and one dendron, both bearing a sulfur atom close to the surface, scored best in the activity–toxicity relationship analysis and were chosen for resistance assays. No changes in the inhibitory and bactericidal capacity in the case of the dendron and only a slight increase of these values for the dendrimer were observed after 15 subculture cycles. Furthermore, these two compounds remained active towards different strains of resistant bacteria, including multi-resistent S. aureus, and avoided formation of biofilms at concentrations over the minimum inhibitory concentration (MIC).