Antibacterial and toxicological evaluation of (E)-2-((3,7-dimethylocta-2,6-dien-1-yl)oxy)ethyl acetate.

Abstract

Klebsiella pneumoniae is a Gram-negative bacterium of great clinical relevance, responsible for severe infections and frequently associated with multidrug resistance. In this context, the synthesis of derivatives from natural products emerges as a promising alternative for the development of new compounds with biological and pharmacological potential. In the search for new compounds, the present study aimed to evaluate the antibacterial activity of (E)-2-((3,7-dimethylocta-2,6-dien-1-yl)oxy)ethyl acetate against K. pneumoniae strains. To achieve this goal, in silico methodologies were employed using the software PASS online®, Molinspiration®, admetSAR®, and molecular docking. For the in vitro studies, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined using 96-well plates, along with combination tests with conventional synthetic antibacterials through disk diffusion. The main results of this study indicated that TSM-17 exhibited low theoretical toxicity. Through molecular docking, it was possible to observe the interaction of TSM-17 with the enzymatic active site of topoisomerase IV. The MIC of TSM-17 ranged from 250 µg/mL to 500 µg/mL against K. pneumoniae strains, indicating good antimicrobial activity, and it also showed bactericidal activity against most strains. Furthermore, the combination of TSM-17 with conventional antimicrobials, especially tetracycline, gentamicin, and cephalothin, resulted in synergistic effects, enhancing its efficacy. Thus, this study highlights the potential of the TSM-17 compound as a promising candidate for the development of new antibacterial agents against K. pneumoniae and reinforces the relevance of natural product-derived compounds in the search for new therapeutic alternatives to combat antimicrobial resistance.