Evaluation of Antibacterial Activity against Nosocomial Pathogens of an Enzymatically Derived α-Aminophosphonates Possessing Coumarin Scaffold

The purpose of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity against selected strains of multidrug-resistant nosocomial pathogenic bacteria. The previously developed enzyme-catalysed Kabachnik–Fields protocol allowed us to obtain the studied compounds with high yields which were free from metal impurities. The structure–activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF(3)−) in the coumarin scaffold. MIC and MBC studies carried out on six selected pathogenic bacterial strains (Gram-positive pathogenic Staphylococcus aureus (ATCC 23235) strain, as well as on Gram-negative Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), Enterobacter cloacae (ATCC 49141), Porphyromonas gingivalis (ATCC 33277), and Treponema denticola (ATCC 35405)) have shown that tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Furthermore, we have shown that the studied coumarin-based α-aminophosphonates, depending on their structural characteristics, are non-selective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients.