Boronic acids: broad specificity of inhibition of penicillin-binding proteins and β-lactamases conferring bacterial antibiotic resistance

The wide spread of antibiotic-resistant bacterial pathogens has attracted great interest in the development of new drugs to suppress resistance emergence. They include inhibitors of β-lactamases (β-Ls), which confer bacterial resistance to β-lactam antibiotics. This class of antibiotics targets penicillin-binding proteins (PBPs), the inhibition of which leads to the disruption of the bacterial cell wall synthesis. β-Lactamases catalyze the hydrolysis of the amide bond of the β-lactam ring, causing inactivation of the antibiotic. Due to the structural diversity of β-Ls, it is relevant to search for their inhibitors characterized by broad specificity. Boronic acids are a promising class of compounds capable of inhibiting not only different molecular classes of β-Ls but also PBPs. The review considers the data on the mechanisms of interaction of β-lactams with PBPs and β-Ls, as well as on the effect of the structure of boronic acid derivatives on their inhibitory activity against various bacterial enzymes. Combinations of antibacterial drugs with β-L inhibitors that simultaneously inhibit PBPs are promising for overcoming antibiotic resistance of different pathogens.