Design and synthesis of caffeic acid derivatives and evaluation of their inhibitory activity against Pseudomonas aeruginosa

Bacteria need to transmit autoinducers to each other through a quorum sensing system. When the concentration of signal molecule reaches a threshold, it affects the expression of specific genes in bacteria, thereby improving the resistance of bacteria to antibiotics, promoting the formation of biofilms, and producing virulence factors. In this paper, various caffeic acid derivatives were synthesized based on functional groups. The results of growth curve and minimal inhibitory concentration proved that the derivatives did not affect the growth of Pseudomonas aeruginosa . Therefore, the inhibitory effects of the derivatives on biofilms and virulence factors were further evaluated. Among these derivatives examined, compound F-17 (4-bromophenethyl-3-(3, 4-dihydroxy-phenyl)acrylate) showed very significant inhibitory effect on biofilm, elastase, pyocyanin, and swarming motility. Molecular docking and calculation of binding free energy of F-17 also showed a good binding effect on LasR and PqsR. In addition, compound F-17 has no obvious cytotoxicity. These experimental results show that F-17 is a potential virulence factor inhibitor. A series of derivatives were synthesized based on caffeic acid. F-17 has good biofilm inhibition and quorum sensing inhibition activities against Pseudomonas aeruginosa , and can be used as quorum sensing inhibitor.