Avaliação do efeito antibacteriano sobre cepas de Klebsiella pneumoniae e perfil citotóxico da 2-cloro-N-(4-flúor-3-nitrofenil)acetamida

Abstract

Klebsiella pneumoniae bacteria are opportunistic pathogens of great clinical relevance. It is estimated that this species is responsible for approximately one third of the total infections caused by Gram-negative bacteria in general. It is also an important biofilm-forming species and a source of antibiotic resistance, which poses challenges in the treatment of infections caused by the species. Health agencies emphasize the critical need to develop new drugs to fight infections caused by this pathogen. Studies have shown antimicrobial potential of acetamide derivatives, however, 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide is a substance belonging to this group for which there are still no reports of antibacterial activity found in the literature. Based on this, the objective of this study was to evaluate the antibacterial effect of the substance on K. pneumoniae strains and also to analyze its cytotoxic profile. The Minimum Inhibitory Concentration (MIC) was 512 μg/mL against all strains of K. pneumoniae used in the study. The substance showed bactericidal activity from the MIC, with Minimum Bactericidal Concentration (MBC) also 512 μg/mL. The analysis by molecular docking suggests the action on the bacterial cell wall and the chloro present in the chemical structure helps in the stabilization of the molecule at the active site, such data being reinforced by the observation of cell lysis promoted by acetamide in vitro. Cell death of K. pneumoniae strains was also observed after 6 hours of treatment at 1024 μg/ mL of acetamide concentration. The cytotoxic and mutagenic effects in vitro, as well as the assessment of pharmacokinetic parameters in silico, suggest good potential for future analysis of in vivo application. 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide resulted in favorable effects when administered in combination with antibacterials, promoting additivity and synergism of action on K. pneumoniae. In addition, a pronounced antibiofilm effect was observed, the substance being able to act effectively on biofilms formed by the species. Thus, this work serves as a basis for future perspectives to be drawn on the clinical application of 2-chloro-N-(4-fluoro-3-nitrophenyl)acetamide in the treatment of infections caused by K. pneumoniae.