Antibacterial and anti-biofilm activities of cinchona alkaloid derivatives against Staphylococcus aureus

Biofilms is the predominant bacterial lifestyle in nature and they are resistant to commonly available antibacterials. Thus, an enormous need exists to find new effective anti-biofilm therapy. Here a library of cinchona alkaloids was screened for activity against Staphylococcus aureus biofilms. Crystal violet and resazurin assays were used to measure effects on biomass and viability, respectively. One derivative, 11-TPSCD (structure), was found effective against planktonic bacteria and in preventing biofilm formation (IC₅₀ ˜ 6µM) but higher concentrations were required to eradicate mature biofilms. An exploration of the chemical space occupied by the active derivative (red dot) in comparison to the cinchona alkaloid library and the structurally related quinolone antibiotics was made using the principal component analysis (PCA)-based model ChemGPS-NP. The results suggest that another interesting region exists for antibacterial and anti-biofilm activity that can be populated by quinine-type antimicrobials, outside of the one defined by quinolone antibiotics.