Efficacy of new 5-nitroimidazoles against metronidazole-susceptible and -resistant Giardia, Trichomonas, and Entamoeba spp.

The efficacies of 12 5-nitroimidazole compounds and I previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via S(RN)1 and subsequent reactions, were assayed against the protozoan par asites Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica . Two metronidazole sensitive lines and two metronidazole-resistant lines o f Giardia and one line each of metronidazole-sensitive and -resistant Trich omonas were tested. All except one of the compounds were as effective or mo re effective than metronidazole against Giardia and Trichomonas, but none w as as effective overall as the previously described 2-lactam-substituted 5- nitroimidazole. None of the compounds was markedly more effective than metr onidazole against Entamoeba, Significant cross-resistance between most of t he drugs tested and metronidazole was evident among metronidazole-resistant lines of Giardia and Trichomonas, However, some drugs were lethal to metro nidazole-resistant Giardia and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasize s the potential in developing new nitroimidazole drugs which are more effec tive than metronidazole and which may prove to be useful clinical alternati ves to metronidazole.