Susceptibility of Helicobacter pylori and Pharmacokinetic Properties in Mice of New 5-Nitroimidazole Derivatives Devoid of Mutagenic Activity in the Ames Test

Summary

The minimum inhibitory concentrations of metronidazole and four new 5-nitroimidazole derivatives (EU 11100, EU 11102, EU 11103, EU 11104), obtained by the reaction of 1-methyl-5-nitroimidazolyl-2-carboxyaldehyde and terbutylphenol, were determined against 25 clinical isolates of Helicobacter pylori. Three of them (EU 11100, EU 11103, EU 11104) exhibited an antibacterial activity higher than that of metronidazole. The last one, the molecule EU 11102, was less active than metronidazole.

In mice, after a single equimolar oral administration, the molecules EU 11100 and 11103 were poorly absorbed and poorly excreted in urine. The molecule EU 11104 was well adsorbed and its urinary recovery was slightly lower than that of metronidazole. The substance EU 11102 was not demonstrable in blood and urine.

In the Salmonella/microsome mutagenicity test only the molecule EU 11100 showed an increase of mutation frequency in S.typhimurium TA 100.

Key words:

• nitroimidazole
• Helicobacter pylori
• pharmacokinetic
• mutagenicity