In vitro Antimicrobial Activity of Amiloride Analogs against Pseudomonas

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Abstract
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 HC1, 5-(N-N-dimethyl)amiloride HC1 (DMA), 5-(N, N-hexamethylene)ami-loride HC1 (HMA), and 5-(N-methyl-N-isobutyl)amiloride HC1 (MIA) on 30 Pseudomonas strains (20 P. aeruginosa and 10 P. cepacia) were compared to amiloride HC1 after a 24-hour incubation in Mueller-Hinton broth at 35 °C. At pH 7.3 the MIC range and MIC50 (in mg/l; MIC50 in parentheses) for amiloride HC1, benzamil HC1, 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 antipseudomo-nal agents in vitro than amiloride, with the more lipophilic compounds HMA and MIA, having the most profound activity.

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