Studies on antiparasitic agents: effect of the lactam nucleus substitution in the 2-position on the in-vitro activity of new 5-nitroimidazoles

Abstract

The in-vitro antiprotozoal activity of a series of new 5-nitroimidazoles substituted in the 2-position via a lactam nucleus was studied. All these compounds exhibited a better effect than metronidazole and structure-activity relationships are discussed.

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

“…or more effective than metronidazole against some or all organisms tested. The lactam-substituted compound (compound 13) was significantly more effective than metronidazole against Giardia (50 to 100 times more effective) and Trichomonas (50 times more effective), but against the Entamoeba strain that we used the compound was not as effective as it was previously (30). Compound 3 was uniformly less effective than metronidazole on every occasion in which it was tested, showing that the substitution on the imidazole ring by an acyl group resulted in a loss of antiprotozoal activity.…”

“…As a consequence, they are especially valuable for the synthesis of a large number of complex and highly branched compounds. Recently, 5-nitroimidazole derivatives including the lactam-substituted nitroimidazole have been shown to be significantly more effective antiprotozoal agents than metronidazole (8,30). In the study described here we examined the activities of other new 5-nitroimidazole compounds against metronidazole-sensitive and -resistant G. duodenalis (synonymous with Giardia lamblia and Giardia intestinalis) and T. vaginalis and against E. histolytica, the three most medically important anaerobic protozoa.…”

The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review

“…This disease is manifested by chronic diarrhea and poor nutritional absorption, and its transmission takes place through the fecal-oral route. For many years, metronidazole has been the drug of choice for the pharmacological treatment of giardiasis, but recently, the most commonly used drugs include benzimidazoles, nitrofuranes, quinacrine, and macrocyclic lactones [114][115][116]. However, there is an impelling need to find new antiparasitics against G. lamblia because of the increasing therapeutic failure due to low compliance with drug therapy, re-infestation, and drug resistance to metronidazole and its related derivatives [117].…”

Designing New 5-Nitroimidazoles: Towards Safer Anti-infectious Agents

“…Indeed, this compound possessed an anti-trichomonas activity (IC 50 = 10.8 µM) close to those of ronidazole and metronidazole (IC 50 = 2.33 µM), while showing only 4% of the mutagenicity of metronidazole and 0.28% of the mutagenicity of ronidazole. Focusing our attention on 5-nitroimidazoles and their reactivity towards S RN 1,our group was able to synthesize the pyrrolidine derivative RP 57967, which has proved to be particularly active on Trichomonas vaginalis and Entamoeba histolytica [25][26][27].The 1-methyl-3-[(1-methyl-5-nitro-1H-imidazol-2-yl)methylene]pyrrolidin-2-one RP 57967 is very active on anaerobic bacteria, more active than metronidazole and dimetridazole. This molecule was prepared by S RN 1 reaction of 2-chloromethyl-1-methyl-5-nitro-1H-imidazole with 1-methyl-3-nitropyrrolidin-2-one lithium salt, followed by elimination of nitrous acid (Scheme 1).…”