Syntheses of Six Tetronamides and Evaluation as Biofilm Inhibitors against the Citrus Canker Bacterial-Pathogen Xanthomonas citri ssp. citri

Small molecules from the family of gamma-lactones have a wide variety of biological activities, including antibiotics and biofilm inhibitors against bacterial pathogens. In the present study, a group of six beta-arylamino-gamma-lactones known as tetronamides were synthesized from reduced mucobromic acid and different anilines (38-77%). The compounds were characterized by IR, 1H NMR, 13C NMR, and mass spectrometry (MS). The six tetronamides were evaluated for antimicrobial and antibiofilm activity against the plant bacterial pathogen Xanthomonas citri ssp. citri (Xcc), which causes citrus canker, one of the most devastating citrus diseases worldwide. Four compounds (3b, 3d, 3e, and 3f) showed a minimum inhibitory concentration (MIC) against Xcc of 500 mu g/mL, while the other two (3a and 3c) had a MIC against Xcc of 1000 mu g/mL. The bacterial biofilm inhibition activity was evaluated by testing the concentrations between 0 and 125 mu g/mL. The results showed that all the six compounds inhibited the biofilm formation at concentrations lower than MIC. The best performances in biofilm inhibition were recorded for the compounds with the presence of a halogen on the aromatic ring (3b, 3e, and 3f), displaying a median biofilm inhibition concentration (IC50) of 15.4 mu g/mL. This study suggested that tetronamides have potential as Xcc biofilm inhibitor to control citrus canker alone or together with other antimicrobials.