Activity of Cinnamic Acid Derivatives with 4-Chloro-2-mercaptobenzenesulfonamide Moiety against Clinical HLAR and VRE Enterococcus spp

The rapid increase in strains that are resistant to antibiotics requires new active compounds to be found whose mechanism of action on bacteria is different to those that are currently known. Of particular interest are compounds that occur in plants as secondary metabolites. The focus of this study concerns the examination of the effects of synthetic cinnamic acid derivatives, with 4-chloro-2-mercaptobenzenesulfonamide moiety on spp. with HLAR (high-level aminoglycoside resistance) and VRE (vancomycin-resistant ) mechanisms. The minimum inhibitory concentration (MIC) values of the tested compounds were determined using the serial dilution method for spp. groups, and the most active compounds were as follows: , , , and (2-4 µg/mL). These compounds, at a concentration of 4 × MIC, inhibited the biofilm formation of HLAR strains (70 to 94%). At concentrations of 2 × MIC and 4 × MIC, they also inhibited the growth of VRE strains (42 to 96%). The best effect produced on the formed biofilm was demonstrated by compound (from 62% MIC concentration to 89% 4 × MIC concentration) on the tested HLAR strains. In vitro studies, using the peripheral blood of domestic sheep, demonstrated the stable bacteriostatic activity of the tested compounds against spp. The compounds , , , and showed synergism and additivity with ampicillin, streptomycin, gentamicin and vancomycin against resistant strains of spp. The tested compounds, when combined, reduce the MIC for antibiotics by 800 to 10,000 times for HLAR strains and by 8 to 10,000 times for VRE strains. The MIC of the tested compounds, in combination with antibiotics, is reduced 2-16-fold for HLAR strains and 2-32-fold for VRE strains. These studies demonstrate the potential for the therapeutic use of synthetic, cinnamic acid derivatives, with 4-chloro-2-mercaptobenzenesulfonamide moiety, to work against clinical strains of spp.