In vitro inhibitory activities of urea analogues on bacterial urease

Abstract

Twenty six urea analogues, most of which have already been approved for human use, were tested for their antiurease activityin vitro. Cell-free extracts obtained from a clinical isolate ofProteus mirabilis was used as the source of enzyme. Acetohydroxamic acid which is a proven potent urease inhibitor but not approved for human use was again shown to be the most active compound among the tested. Phenacemide, cycloserine, and deferoxamine were demonstrated to be moderate inhibitors. Oxytetracycline, trimethoprim and cefamandole revealed a demonstrable antiruease activity, but only at very high concentrations. The antiurease activity of cycloserine, trimethoprim, and cefamandole was pH dependent; only active at acidic pH. The inhibitory activity of acetohydroxamic acid however was independent of change in pH. Hydrogen ion concentration plays an important role in urease activity and acidification (pH 5.5) alone eliminates approximately 65% of the enzymic activity. Adjustment of pH therefore appears to be an important adjunct in reducing urease activity and should always be studied to maximize the efficacy of antiurease compounds under investigation.