Triterpene derivatives as relevant scaffold for new antibiofilm drugs

Abstract

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 biofilmcells (gram-positive bacterial pathogens: Enterococcus faecalis, Staphylococcus aureus and Staphylococcus epidermidis). We evaluated the antibiofilmactivity (through the crystal violet method), as well as the antibacterial activity via absorbance (OD600) at concentrations of 5, 25 and 100 M. Likewise, the cytotoxicity of all compoundswas evaluated on a kidney African greenmonkey (VERO) cell line at the same concentration, byMTT (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.