Release of virulence factors in Pseudomonas aeruginosa is regulated by two N- acylhomoserine lactones, PAI-1 and PAI-2, that activate the respective transcription factors LasR and RhlR. With the goal of developing novel therapeutic agents, we synthesized constrained analogs of PAI-1 and evaluated them in P. aeruginosa. Two of the novel analogs bound to LasR and showed agonist activity in LasR stimulation of a lasI-lacZ ...