Nitroxides as anti-biofilm compounds for the treatment of Pseudomonas aeruginosa and mixed-culture biofilms

Abstract

A series of 23 nitroxides (5–27) was tested for biofilm modulatory activity using a crystal violet staining technique. 3-(Dodecane-1-thiyl)-4-(hydroxymethyl)-2,2,5,5-tetramethyl-1-pyrrolinoxyl (22) was found to significantly suppress biofilm formation and elicit dispersal events in both Pseudomonas aeruginosa and mixed-culture biofilms. Twitching and swarming motilities were enhanced by nitroxide 22, leaving the planktonic-specific swimming motility unaffected and suggesting that the mechanism of 22-mediated biofilm modulation is linked to the hyperactivation of surface-associated cell motilities. Preliminary structure–activity relationship studies identify the dodecanethiyl chain, hydroxymethyl substituent and the free radical moiety to be structural features pertinent to the anti-biofilm activity of 22.