Enzymatic Synthesis of a Novel Coumarin Aminophosphonates: Antibacterial Effects and Oxidative Stress Modulation on Selected E. coli Strains

The objective of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and alpha-amino dimethyl phosphonate moieties, on antimicrobial activity toward selected LPS-varied E. coli strains. Studied antimicrobial agents were prepared via a Kabachnik-Fields reaction promoted by lipases. The products were provided with an excellent yield (up to 92%) under mild, solvent- and metal-free conditions. A preliminary exploration of coumarin alpha-amino dimethyl phosphonate analogs as novel antimicrobial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The structure-activity relationship revealed that an inhibitory activity of the synthesized compounds is strongly related to the type of the substituents located in the phenyl ring. The collected data demonstrated that coumarin-based alpha-aminophosphonates can be potential antimicrobial drug candidates, which is particularly crucial due to the constantly increasing resistance of bacteria to commonly used antibiotics.

Automated summary

The study aimed to assess the synergistic effect of coumarin and alpha-amino dimethyl phosphonate moieties, two important pharmacophores, on antimicrobial activity against different strains of E. coli with varied lipopolysaccharide (LPS). The antimicrobial agents were prepared through a lipase-promoted Kabachnik-Fields reaction, with excellent yield (up to 92%) achieved under mild, solvent- and metal-free conditions. Preliminary exploration of coumarin alpha-amino dimethyl phosphonate analogs as novel antimicrobial agents revealed that the substituents on the phenyl ring strongly influenced the inhibitory activity. The data collected suggested that coumarin-based alpha-aminophosphonates could serve as potential antimicrobial drug candidates, which is crucial due to the increasing resistance of bacteria to commonly used antibiotics.