ArticlePloS one2013
High sensitivity of Giardia duodenalis to tetrahydrolipstatin (orlistat) in vitro.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- Arginine metabolism has a pivotal function for the encystation of Giardia duodenalis.PLoS pathogens · 2026Article
- Interplay of obesity and parasitic infection: current evidence of immunogenesis, tumorigenesis and leptin receptor involvement.Nutrition & metabolism · 2025Review
- Phospholipases A and Lysophospholipases in protozoan parasites.Microbial cell (Graz, Austria) · 2023Review
- Prevalence of Intestinal Parasitic Infections, Genotypes, and Drug Susceptibility ofTropical medicine and infectious disease · 2023Article
- Ultrastructural Alterations of the Human PathogenPathogens (Basel, Switzerland) · 2023Review
- Highly contiguous genomes of human clinical isolates ofMicrobial genomics · 2023Article
- Draft genome sequence of3 Biotech · 2023Article
- 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
- Current Therapy and Therapeutic Targets for Microsporidiosis.Frontiers in microbiology · 2022Review
- Know your enemy - transcriptome of myxozoanParasitology · 2021Article
- Suitability of current typing procedures to identify epidemiologically linked human Giardia duodenalis isolates.PLoS neglected tropical diseases · 2021Article
- Article
- Stereochemical Structure Activity Relationship Studies (S-SAR) of Tetrahydrolipstatin.ACS medicinal chemistry letters · 2018Article
- 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
- Myosin-independent cytokinesis inProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Drug Development Against the Major Diarrhea-Causing Parasites of the Small Intestine, Cryptosporidium and Giardia.Frontiers in microbiology · 2015Review
- Total synthesis of tetrahydrolipstatin and stereoisomers via a highly regio- and diastereoselective carbonylation of epoxyhomoallylic alcohols.Journal of the American Chemical Society · 2014Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Giardiasis, a gastrointestinal disease caused by Giardia duodenalis, is currently treated mainly with nitroimidazoles, primarily metronidazole (MTZ). Treatment failure rates of up to 20 percent reflect the compelling need for alternative treatment options. Here, we investigated whether orlistat, a drug approved to treat obesity, represents a potential therapeutic agent against giardiasis. We compared the growth inhibitory effects of orlistat and MTZ on a long-term in vitro culture adapted G. duodenalis strain, WB-C6, and on a new isolate, 14-03/F7, from a patient refractory to MTZ treatment using a resazurin assay. The giardiacidal concentration of the drugs and their combined in vitro efficacy was determined by median-effect analysis. Morphological changes after treatment were analysed by light and electron microscopy. Orlistat inhibited the in vitro growth of G. duodenalis at low micromolar concentrations, with isolate 14-03/F7 (IC50(24h) = 2.8 µM) being more sensitive than WB-C6 (IC50(24h) = 6.2 µM). The effect was significantly more potent compared to MTZ (IC50(24h) = 4.3 µM and 11.0 µM, respectively) and led to specific undulated morphological alterations on the parasite surface. The giardiacidal concentration of orlistat was >14 µM for 14-03/F7 and >43 µM for WB-C6, respectively. Importantly, the combination of both drugs revealed no interaction on their inhibitory effects. We demonstrate that orlistat is a potent inhibitor of G. duodenalis growth in vitro and kills parasites at concentrations achievable in the gut by approved treatment regimens for obesity. We therefore propose to investigate orlistat in controlled clinical studies as a new drug in giardiasis.
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