Imide-based enones: A new scaffold that inhibits biofilm formation in Gram-negative pathogens

Abstract

We prepared a series of enones containing different substituents as potential antibiofilm molecules. The design considered the structural features previously found in N-acylhomoserine lactones, but it replaced the labile furanone with different imides portions. After evaluation, some of the analogs inhibited 50 % or more the formation of the biofilm from P. aeruginosa or A. baumannii; moreover, substituents attached at the phenyl ring, the size of the enone as well as the type of imide seemed relevant for the selectivity against the tested pathogens. In the end, we performed a molecular docking study using the crystallized LasR to describe the main interactions of the ligand-receptor complex and propose a plausible mechanism of action.