ArticleInternational journal for parasitology. Drugs and drug resistance2012
Nitroimidazole drugs vary in their mode of action in the human parasite Giardia lamblia.
Article in International journal for parasitology. Drugs and drug resistance, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 58 citations in OpenAlex.
- Structure-enabled enhancement of potency in a metronidazole-benznidazole hybrid: design, synthesis, and evaluation of antitrypanosomal activity of a benzylamide-linked 5-nitroimidazole.Frontiers in pharmacology · 2026Article
- Nitazoxanide Analogs: Synthesis, In Vitro Giardicidal Activity, and Effects onInternational journal of molecular sciences · 2025Article
- Fused Enzyme Glucose-6-Phosphate Dehydrogenase::6-Phosphogluconolactonase (G6PD::6PGL) as a Potential Drug Target inMicroorganisms · 2024Review
- Nitazoxanide Inhibits the Bifunctional Enzyme GlG6PD::6PGL ofInternational journal of molecular sciences · 2023Article
- Ultrastructural Alterations of the Human PathogenPathogens (Basel, Switzerland) · 2023Review
- Review
- Mass Spectrometry-Based Metabolomics Revealed Effects of Metronidazole onPharmaceuticals (Basel, Switzerland) · 2023Article
- Cellular mechanism of action of 2-nitroimidazoles as hypoxia-selective therapeutic agents.Redox biology · 2022Article
- Different Drugs, Same End: Ultrastructural Hallmarks of Autophagy in Pathogenic Protozoa.Frontiers in microbiology · 2022Review
- Characterization of Metronidazole-ResistantFrontiers in microbiology · 2022Article
- Identification of proteins and cellular pathways targeted by 2-nitroimidazole hypoxic cytotoxins.Redox biology · 2021Article
- Article
- Chromosomal Resistance to Metronidazole in Clostridioides difficile Can Be Mediated by Epistasis between Iron Homeostasis and Oxidoreductases.Antimicrobial agents and chemotherapy · 2020Article
- Giardia lamblia: Laboratory Maintenance, Lifecycle Induction, and Infection of Murine Models.Current protocols in microbiology · 2020Article
- Click chemistry-facilitated comprehensive identification of proteins adducted by antimicrobial 5-nitroimidazoles for discovery of alternative drug targets against giardiasis.PLoS neglected tropical diseases · 2020Article
- Metronidazole and Secnidazole Carbamates: Synthesis, Antiprotozoal Activity, and Molecular Dynamics Studies.Molecules (Basel, Switzerland) · 2020Article
- Activity of methylgerambullin from Glycosmis species (Rutaceae) against Entamoeba histolytica and Giardia duodenalis in vitro.International journal for parasitology. Drugs and drug resistance · 2019Article
- Genetic variation in metronidazole metabolism and oxidative stress pathways in clinicalInfection and drug resistance · 2019Article
- Proteomic and functional analyses reveal pleiotropic action of the anti-tumoral compound NBDHEX in Giardia duodenalis.International journal for parasitology. Drugs and drug resistance · 2017Article
- Click Chemistry-Facilitated Structural Diversification of Nitrothiazoles, Nitrofurans, and Nitropyrroles Enhances Antimicrobial Activity against Giardia lamblia.Antimicrobial agents and chemotherapy · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Giardia lamblia (syn. duodenalis, intestinalis) is a globally occurring micro-aerophilic human parasite that causes gastrointestinal disease. Standard treatment of G. lamblia infections is based on the 5-nitroimidazole drugs metronidazole and tinidazole. In two other micro-aerophilic parasites, Entamoeba histolytica and Trichomonas vaginalis, 5-nitroimidazole drugs bind to proteins involved in the thioredoxin-mediated redox network and disrupt the redox equilibrium by inhibiting thioredoxin reductase and depleting intracellular thiol pools. The major aim of this study was to assess whether nitroimidazoles exert a similar toxic effect on G. lamblia physiology. The 5-nitroimidazoles metronidazole and tinidazole were found to bind to the same subset of proteins including thioredoxin reductase. However, in contrast to E. histolytica and T. vaginalis, none of the other proteins bound are candidates for being involved in the thioredoxin-mediated redox network. Translation elongation factor EF-1γ, an essential factor in protein synthesis, was widely degraded upon treatment with 5-nitroimidazoles. 2-Nitroimidazole (azomycin) and the 5-nitroimidazole ronidazole did not bind to any G. lamblia proteins, which is in contrast to previous findings in E. histolytica and T. vaginalis. All nitroimidazoles tested reduced intracellular thiol pools in G. lamblia, but metronidazole, also in contrast to the situation in the other two parasites, had the slightest effect. Taken together, our results suggest that nitroimidazole drugs affect G. lamblia in a fundamentally different way than E. histolytica and T. vaginalis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.