ArticleAntimicrobial agents and chemotherapy2014
Giardial triosephosphate isomerase as possible target of the cytotoxic effect of omeprazole in Giardia lamblia.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Selective Anti-Giardial Action of Indirubin: Biochemical and Functional Evidence for Inhibition of Triosephosphate Isomerase and Aldose Reductase inInternational journal of molecular sciences · 2026Article
- Omeprazole as a Novel Treatment Option for Giardiasis in Cats.Veterinary medicine and science · 2026Article
- Nitazoxanide Analogs: Synthesis, In Vitro Giardicidal Activity, and Effects onInternational journal of molecular sciences · 2025Article
- Expanding the antiprotozoal activity and the mechanism of action of n-butyl and iso-butyl ester of quinoxaline-1,4-di-Journal of enzyme inhibition and medicinal chemistry · 2024Article
- TATA-Binding Protein-Based Virtual Screening of FDA Drugs Identified New Anti-Giardiasis Agents.International journal of molecular sciences · 2024Article
- Repurposing of rabeprazole as an anti-Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Ultrastructural changes and IgA modulatory effect of commercial prebiotic and probiotic in murine giardiasis.Journal of parasitic diseases : official organ of the Indian Society for Parasitology · 2023Article
- Pyridyl Methylsulfinyl Benzimidazole Derivatives as Promising Agents againstMolecules (Basel, Switzerland) · 2022Article
- Antigiardial Activity of Novel Guanidine Compounds.ChemMedChem · 2022Article
- An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives.Frontiers in cellular and infection microbiology · 2022Review
- Multilevel Approach for the Treatment of Giardiasis by Targeting Arginine Deiminase.International journal of molecular sciences · 2021Article
- Enhanced Antigiardial Effect of Omeprazole Analog Benzimidazole Compounds.Molecules (Basel, Switzerland) · 2020Article
- Deamidated Human Triosephosphate Isomerase is a Promising Druggable Target.Biomolecules · 2020Article
- Characterisation of the in vitro activity of a Nitazoxanide-N-methyl-1H-benzimidazole hybrid molecule against albendazole and nitazoxanide susceptible and resistant strains of Giardia intestinalis and its in vivo giardicidal activity.Memorias do Instituto Oswaldo Cruz · 2020Article
- Assessment of the potential therapeutic effects of omeprazole in Schistosoma mansoni infected mice.Parasitology research · 2019Article
- On the molecular and cellular effects of omeprazole to further support its effectiveness as an antigiardial drug.Scientific reports · 2019Article
- The Possible Role ofFrontiers in oncology · 2019Review
- First characterization of a microsporidial triosephosphate isomerase and the biochemical mechanisms of its inactivation to propose a new druggable target.Scientific reports · 2018Article
- Treatment-refractory giardiasis: challenges and solutions.Infection and drug resistance · 2018Review
- Disulfiram as a novel inactivator of Giardia lamblia triosephosphate isomerase with antigiardial potential.International journal for parasitology. Drugs and drug resistance · 2017Article
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Giardiasis is highly prevalent in the developing world, and treatment failures with the standard drugs are common. This work deals with the proposal of omeprazole as a novel antigiardial drug, focusing on a giardial glycolytic enzyme used to follow the cytotoxic effect at the molecular level. We used recombinant technology and enzyme inactivation to demonstrate the capacity of omeprazole to inactivate giardial triosephosphate isomerase, with no adverse effects on its human counterpart. To establish the specific target in the enzyme, we used single mutants of every cysteine residue in triosephosphate isomerase. The effect on cellular triosephosphate isomerase was evaluated by following the remnant enzyme activity on trophozoites treated with omeprazole. The interaction of omeprazole with giardial proteins was analyzed by fluorescence spectroscopy. The susceptibility to omeprazole of drug-susceptible and drug-resistant strains of Giardia lamblia was evaluated to demonstrate its potential as a novel antigiardial drug. Our results demonstrate that omeprazole inhibits giardial triosephosphate isomerase in a species-specific manner through interaction with cysteine at position 222. Omeprazole enters the cytoplasmic compartment of the trophozoites and inhibits cellular triosephosphate isomerase activity in a dose-dependent manner. Such inhibition takes place concomitantly with the cytotoxic effect caused by omeprazole on trophozoites. G. lamblia triosephosphate isomerase (GlTIM) is a cytoplasmic protein which can help analyses of how omeprazole works against the proteins of this parasite and in the effort to understand its mechanism of cytotoxicity. Our results demonstrate the mechanism of giardial triosephosphate isomerase inhibition by omeprazole and show that this drug is effective in vitro against drug-resistant and drug-susceptible strains of G. lamblia.
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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.