New benzyldiazepane derivatives able to reduce biofilm formation in Escherichia coli

Area of Science:

• Microbiology
• Medicinal Chemistry
• Pharmacology

Background:

• Antimicrobial resistance (AMR) is a major global health threat.
• Bacterial biofilms exacerbate AMR by protecting microbes from antibiotics and host defenses.
• Sub-inhibitory antibiotic concentrations, like chloramphenicol (CHL), can paradoxically promote biofilm development.

Purpose of the Study:

• To synthesize novel benzyldiazepane derivatives as potential anti-biofilm agents.
• To evaluate the efficacy of these compounds in inhibiting biofilm formation in Escherichia coli K-12.
• To assess the synergistic effects of these derivatives when combined with chloramphenicol.

Main Methods:

• Synthesis of benzyldiazepane derivatives.
• Determination of minimum inhibitory concentration (MIC) values.
• Assessment of biofilm inhibition by compounds alone and in combination with sub-inhibitory CHL against E. coli K-12.

Main Results:

• Four synthesized compounds demonstrated intrinsic anti-biofilm activity.
• Nearly all derivatives exhibited a combinatorial anti-biofilm effect with CHL.
• Nitrobenzyl derivative 2 notably reduced biofilm formation both independently and with CHL.

Conclusions:

• Benzyldiazepane derivatives represent a promising scaffold for developing novel anti-biofilm agents.
• These compounds effectively decrease bacterial biofilm formation, offering a strategy against AMR.
• The synergistic activity with CHL enhances the potential of these derivatives in therapeutic applications.