Antibacterial and Antibiofilm Properties of (E,E)-Farnesol Diamine-Derivatives: Potential New Agents Against Methicillin-Resistant Staphylococcus aureus and Escherichia coli.

INTRODUCTION: Antimicrobial resistance, particularly when associated with biofilm formation, represents a major global health challenge. In this context, this study aimed to design, synthesize, and evaluate the in vitro biological activity of (E,E)-farnesylethane-1,2-diamine (4a) and (E,E)-farnesylpiperazine (4b), as dihydrochloride salts. METHODOLOGY: The compounds were synthesized following literature protocols. Their antibacterial activity was evaluated by determining Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) against Staphylococcus aureus (ATCC 25923), methicillinresistant S. aureus (HU25), and Escherichia coli (ATCC 25922). Biofilm formation was evaluated under subinhibitory conditions by quantifying biomass and viable cells. Experiments were conducted in triplicate and analyzed statistically. Biofilm morphology was examined using Scanning Electron Microscopy (SEM). RESULTS: (E,E)-Farnesol exhibited activity against Gram-positive strains (MIC 64 μg/mL for ATCC 25923 and 32 μg/mL for HU25), with no bactericidal effect (MBC >512 μg/mL), indicating a bacteriostatic profile. In contrast, derivatives 4a and 4b displayed bactericidal activity against both Gram-positive and Gram-negative strains (MIC/MBC 32-64 μg/mL; MBC/MIC = 1). In biofilm assays, compound 4b reduced viable cell counts by over 90% across all strains (P < 0.001), while 4a showed moderate inhibition. SEM analysis confirmed reduced biofilm density and morphological alterations, particularly in Gram-positive bacteria. DISCUSSION: Structural modification of (E,E)-farnesol significantly enhanced antibacterial and antibiofilm activity. Its derivatives demonstrate therapeutic potential against multidrug-resistant bacteria. Limitations include restriction to in vitro assays; further in vivo and cytotoxicity studies are needed. CONCLUSION: Compounds 4a and 4b emerge as promising candidates for further development, although additional in vivo and toxicity studies are required.