Effect of methylpyrazoles and coumarin association on the growth of Gram-negative bacteria

One approach to overcome the antimicrobial resistance of many pathogens is to associate compounds with antimicrobial properties and obtain combinations superior compared to the effect of each compound. To identify a possible potentiating effect, we tested and analyzed the inhibitory effect of the combination of coumarin with two pyrazole derivatives, 1,1'-methandiylbis (3,5-dimethyl-1H-pyrazole (AM4) and 3,5-dimethyl-1H-pyrazol-1-yl) methanol 3,5-dimethyl-1-hydroxymethylpyrazol (SAM4). A clear synergistic effect was recorded when coumarin was associated with SAM4, in which case the Fractional Inhibitory Concentration Index (FICI) had a value equal to 0.468 for Citrobacter freundii, Proteus mirabilis, and E. coli. In the other cases, however, both the association between coumarin and AM4 and coumarin SAM4 had only an additive effect (FICI = 0.937-1.00). The bactericidal effect of the coumarin-pyrazole combination over time was better in all cases compared to the effect of the compounds used separately. The viability of the bacterial cells at sub-inhibitory concentrations of the tested compounds was variable, depending on both the type of compound and the bacterial strain.