Inhibitory Effect on Biofilm Formation of Pathogenic Bacteria Induced by Rubrolide Lactam Analogues

Abstract

A series of 32 novel potential bacterial biofilm inhibitor analogues of rubrolides and their lactam derivatives were synthesized. The compounds were prepared and tested against Staphylococcus aureus and Staphylococcus epidermidis. In general, γ-alkylidene-γ-lactams are more active than the corresponding γ-alkylidene-γ-lactones, and the two derivatives are more effective in inhibiting bacterial planktonic growth (IC50 of 1.8 and 5.6 μg mL-1) than natural rubrolides. Compounds showing little effect on planktonic growth were assayed for their ability to inhibit biofilm formation. As biofilm inhibitors, none of the new compounds were effective against S. epidermidis, whereas the three Z-lactam derivatives were very active against S. aureus (IC50 = 0.9-3.3 μg mL-1). The strong antibiofilm formation activity displayed by some γ-alkylidene-γ-lactams indicates that this may represent a promising class of compounds for the development of novel antimicrobial agents against clinically relevant Gram-positive bacteria.