Anti-pseudomonas activity of 3-nitro-4-phenylfuroxan

Pseudomonas aeruginosa is a microorganism that is well adapted to both clinical and industrial settings, where it can form adherent communities that are difficult to eradicate. New anti-Pseudomonas compounds and strategies are necessary, as the current antimicrobial approaches for the inhibition of biofilm formation and, above all, the eradication of formed biofilms are ineffective. Compounds that belong to the furoxan family, which are well-known NO donors, have recently been shown to display anti-Pseudomonas activity. The present study investigates three furoxan compounds that are substituted at the hetero-ring with electron-withdrawing groups (NO2, CN, CONH2) for their effects on P. aeruginosa PAO1 growth and biofilm formation/dispersal. Of the furoxans tested, only 3-nitro-4-phenylfuroxan (KN455) inhibited the growth of suspended P. aeruginosa PAO1 cultures. Furthermore, KN455 inhibited the formation of both younger and older biofilms with very high yields and thus proved itself to be toxic to planktonic subpopulations. It also displayed moderate eradicating power. The activity of KN455 does not appear to be related to its capacity to release small amounts of NO. Interestingly, the isomer 4-nitro- 3-phenylfuroxan (KN454), included for comparison, displayed a comparable antibiofilm rate, but did not show the same antimicrobial activity against suspended cells and planktonic subpopulations. While hypotheses as to the mechanism of action have been formulated, further investigations are necessary to shed light onto the antimicrobial activity of this furoxan.