Fluorine- and Trifluoromethyl-Substituted Biphenyl Derivatives: Promising Antimicrobial Agents Targeting Escherichia...

This study investigates the synthesis, antibacterial activity, structure-activity relationships (SARs), and molecular docking of F- and CF₃-substituted biphenyl derivatives (5A-5K) as potential antimicrobial agents. Ten novel biphenyl derivatives were synthesized, incorporating trifluoromethyl (CF₃) and fluorine (F) substitutions, to evaluate their efficacy against various bacterial strains, including Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Streptococcus pneumoniae. Antimicrobial assays demonstrated that the F substitution significantly enhanced antibacterial activity, with the bis-F derivative (5D) showing improved potency compared to the other compounds. Molecular docking studies revealed strong binding affinities between the compounds and the target enzyme, Escherichia coli FabH, suggesting a promising mechanism of action. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions indicated favorable drug-like properties for most compounds, with low toxicity and good oral bioavailability. The SAR analysis further confirmed that bis-F substitution at the meta-position of the biphenyl backbone (5D) contributed synergistically to the compounds' antimicrobial efficacy. These findings highlight the potential of these derivatives as novel antibacterial agents.