New medicines for the treatment of bacterial biofilm formation are required. For this reason, this study shows the in vitro activity of betulinic acid (BA), ursolic acid (UA) and their twenty derivatives against planktonic and biofilm cells (gram-positive bacterial pathogens: Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis). We evaluated the antibiofilm activity (through the crystal violet method), as well as the antibacterial activity via absorbance (OD600) at concentrations of 5, 25 and 100 µM. Likewise, the cytotoxicity of all compounds was evaluated on a kidney African green monkey (VERO) cell line at the same concentration, by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) methodology. We verified for the first time whether different groups at carbon 3 (C-3) of triterpenes may interfere in the antibiofilm activity with minimal or no antibacterial effect. After the screening of 22 compounds at three distinct concentrations, we found antibiofilm activity for eight distinct derivatives without antibiotic effect. In particular, the derivative 2f, with an isopentanoyl ester at position C-3, was an antibiofilm activity against S. aureus without any effect upon mammalian cells.
α-Curcumene was isolated from the fresh aerial parts of Senecio selloi Spreng. DC. and its activity against bacteria, yeasts and an alga was inspected by the applying the microdilution method. The strongest effect was manifested against Saccharomyces cerevisiae with estimated values of MIC and MFC 0.8 mg/mL. The α-curcumene synergism in the concentrations of 1 mM and 5 mM, respectively, with selected antibiotics (ciprofloxacin, imipenem, ceftazidim and a combination of amoxicillin and clavulanic acid) was investigated against Staphylococcus aureus, Escherichia coli, Enterobacter cloacae, Staphylococcus haemolyticus and Klebsiella pneumoniae by the disk diffusion assay. The results have shown the occurrence of synergism of α-curcumene with imipenem against the clinical isolate E. cloacae with a significance level of p> 0.05. Based on these informations it can be concluded that fungal strains are more sensitive for α-curcumene than the bacterial ones and the synergism of α-curcumene with imipenem can improve the antibiotic efficiency against the E. cloacae.
1 May 2016 in Bioorganic & Medicinal Chemistry Letters