Synthesis and molecular docking study of α-aminophosphonates as potential multi-targeting antibacterial agents.

ABSTRACT

Antibacterial compounds that reduce extracellular polymeric substances (EPS) are needed to avoid bacterial biofilms in water pipelines. Herein, green one-pot synthesis of α-aminophosphonates (α-Amps) [A-G] was achieved by using ionic liquid (IL) as a Lewis acid catalyst. The synthesized α-Amp analogues were tested against different bacteria such as Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa. The representative [B] analogue showed an efficient antibacterial effect with MIC values of 3.13 µg/mL for E. coli, P. aeruginosa, and 6.25 µg/mL for B. subtilis. Additionally, a strong ability to eliminate the mature bacterial biofilm, with super-MIC values of 12.5 µg/mL for E. coli, P. aeruginosa, and 25 µg/mL for B. subtilis. Moreover, bacterial cell disruption by ROS formation was also tested, and the compound [B] revealed the highest ROS level compared to other compounds and the control, and efficiently destroyed the extracellular polymeric substances (EPS). The docking study confirmed strong interactions between [B] analogue and protein structures with a binding affinity of -6.65 kCal/mol for the lyase protein of gram-positive bacteria and -6.46 kCal/mol for DNA gyrase of gram-negative bacteria. The results showed that α-Amps moiety is a promising candidate for developing novel antibacterial and anti-biofilm agents for clean water supply.