Identification of potential Escherichia coli TEM-1 beta-lactamase inhibitors using catechin backbones as potential Escherichia coli TEM-1 inhibitors

Episodes of bacterial resistance to antibiotics are one of the greatest threats to public health worldwide. Among the main resistance mechanisms identified is the expression of beta-lactamase enzymes in enterobacteria such as Escherichia coli. These enzymes cause resistance to many first-generation beta-lactams and there is a risk of the emergence of new types of betalactamases. Some beta-lactam antibiotics have been successfully introduced on the market in formulations that associate them with inhibitors of these enzymes to prevent their inactivation. Despite the success of this strategy, there are increasing reports of beta-lactamases resistant to these inhibitors. On the other hand, plant-derived metabolites, such as catechins, exhibit several biological actions, including their ability to modulate various bacterial enzymatic activities and generally exhibit low toxicity to humans. Considering the above, the present work evaluated 287 catechins to select the most promising molecules with the potential to inhibit the TEM-1 enzyme of E. coli. The catechin with the highest affinity for TEM-1 according to molecular docking analyses was CHEMBL129482 ((+)-Epicatechin). The results of molecular dynamics, free energy calculation and toxicological predictions show that this molecule presents a promising profile for a next stage of in vitro evaluation.