Efficacy of New 5-Nitroimidazoles against Metronidazole-Susceptible and -Resistant <i>Giardia</i> , <i>Trichomonas</i> , and <i>Entamoeba</i> spp

TLDR

The study synthesized 12 novel 5‑nitroimidazoles and one lactam‑substituted nitroimidazole and tested them against metronidazole‑sensitive and -resistant lines of Giardia duodenalis, Trichomonas vaginalis, and Entamoeba histolytica. Most compounds matched or exceeded metronidazole’s activity against Giardia and Trichomonas, but none surpassed the lactam‑substituted compound, and none were markedly better against Entamoeba, cross‑resistance was common, though some drugs killed metronidazole‑resistant Giardia at lethal concentrations comparable to those for susceptible parasites, underscoring the promise of new nitroimidazoles as clinical alternatives.

Abstract

ABSTRACT The efficacies of 12 5-nitroimidazole compounds and 1 previously described lactam-substituted nitroimidazole with antiparasitic activity, synthesized via S RN 1 and subsequent reactions, were assayed against the protozoan parasites Giardia duodenalis , Trichomonas vaginalis , and Entamoeba histolytica . Two metronidazole-sensitive lines and two metronidazole-resistant lines of Giardia and one line each of metronidazole-sensitive and -resistant Trichomonas were tested. All except one of the compounds were as effective or more effective than metronidazole against Giardia and Trichomonas , but none was as effective overall as the previously described 2-lactam-substituted 5-nitroimidazole. None of the compounds was markedly more effective than metronidazole against Entamoeba . Significant cross-resistance between most of the drugs tested and metronidazole was evident among metronidazole-resistant lines of Giardia and Trichomonas . However, some drugs were lethal to metronidazole-resistant Giardia and had minimum lethal concentrations similar to that of metronidazole for drug-susceptible parasites. This study emphasizes the potential in developing new nitroimidazole drugs which are more effective than metronidazole and which may prove to be useful clinical alternatives to metronidazole.