In vitro antimicrobial activity of amiloride analogs against Pseudomonas

The effects of specific amiloride analogs on Na+ channel and Na+/H+ antiport function in eukaryotic cells have been well studied, but the effect of these agents on Pseudomonas is unknown. The antimicrobial activity of benzamil HCl, 5-(N-N-dimethyl)amiloride HCl (DMA), 5-(N,N-hexamethylene)amiloride HCl (HMA), and 5-(N-methyl-N-isobutyl)amiloride HCl (MIA) on 30 Pseudomonas strains (20 P. aeruginosa and 10 P. cepacia) were compared to amiloride HCl after a 24-hour incubation in Mueller-Hinton broth at 35 degrees C. At pH 7.3 the MIC range and MIC50 (in mg/l; MIC50 in parentheses) for amiloride HCl, benzamil HCl, DMA, HMA and MIA were 400 to > 800 (> 800), 200 to 800 (400), 200 to > 800 (400), 100 to 400 (200), and 100 to 400 (200), respectively, for P. aeruginosa and > 800 (> 800), 400 to > 800 (800), 400 to > 800 (800), 200 to 800 (200), and 200 to 800 (200), respectively, for P. cepacia. Alteration of pH from 5.5 to 8.5 had a slight effect on potency. We conclude that all the analogs studied were more potent antipseudomonal agents in vitro than amiloride, with the more lipophilic compounds HMA and MIA, having the most profound activity.