ArticleAntimicrobial agents and chemotherapy2014
Hsp90 inhibitors as new leads to target parasitic diarrheal diseases.
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 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Review
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- Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis.Antimicrobial agents and chemotherapy · 2024Article
- Systems biology of autophagy in leishmanial infection and its diverse role in precision medicine.Frontiers in molecular biosciences · 2023Review
- A Broad Spectrum Antiparasitic Activity of Organotin (IV) Derivatives and Its Untargeted Proteomic Profiling UsingPathogens (Basel, Switzerland) · 2022Article
- A Bioluminescence-Based Drug Screen Identifies Activities of Fexinidazole and Its Metabolites againstAntibiotics (Basel, Switzerland) · 2022Article
- Structural Basis of Parasitic HSP90 ATPase Inhibition by Small Molecules.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Development of a Machine Learning-Based Cysticidal Assay and Identification of an Amebicidal and Cysticidal Marine Microbial Metabolite againstMicrobiology spectrum · 2022Article
- Disease Biomarkers of Giardiasis.Journal of parasitology research · 2022Review
- The Antifungal Drug Isavuconazole Is both Amebicidal and Cysticidal against Acanthamoeba castellanii.Antimicrobial agents and chemotherapy · 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
- Identification of anisomycin, prodigiosin and obatoclax as compounds with broad-spectrum anti-parasitic activity.PLoS neglected tropical diseases · 2020Article
- Bioactivity of Farnesyltransferase Inhibitors AgainstFrontiers in cellular and infection microbiology · 2019Article
- Larrea tridentata: A novel source for anti-parasitic agents active against Entamoeba histolytica, Giardia lamblia and Naegleria fowleri.PLoS neglected tropical diseases · 2017Article
- 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
- Design, Synthesis and Preliminary Antimicrobial Evaluation ofMedChemComm · 2017Article
- The heat shock protein 90 of Toxoplasma gondii is essential for invasion of host cells and tachyzoite growth.Parasite (Paris, France) · 2017Article
- In vitro and in vivo anti-malarial activity of novel harmine-analog heat shock protein 90 inhibitors: a possible partner for artemisinin.Malaria journal · 2016Article
- Transcriptomic Analysis of the Host Response and Innate Resilience to Enterotoxigenic Escherichia coli Infection in Humans.The Journal of infectious diseases · 2016Article
- The Critical Role of the Cytoskeleton in the Pathogenesis ofCurrent clinical microbiology reports · 2015Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
Entamoeba histolytica and Giardia lamblia are anaerobic protozoan parasites that cause amebiasis and giardiasis, two of the most common diarrheal diseases worldwide. Current therapy relies on metronidazole, but resistance has been reported and the drug has significant adverse effects. Therefore, it is critical to search for effective, better-tolerated antiamebic and antigiardial drugs. We synthesized several examples of a recently reported class of Hsp90 inhibitors and evaluated these compounds as potential leads for antiparasitic chemotherapy. Several of these inhibitors showed strong in vitro activity against both E. histolytica and G. lamblia trophozoites. The inhibitors were rescreened to discriminate between amebicidal and giardicidal activity and general cytotoxicity toward a mammalian cell line. No mammalian cytotoxicity was found at >100 μM for 48 h for any of the inhibitors. To understand the mechanism of action, a competitive binding assay was performed using the fluorescent ATP analogue bis-ANS (4,4'-dianilino-1,1'-binaphthyl-5,5'-disulfonic acid dipotassium salt) and recombinant E. histolytica Hsp90 preincubated in both the presence and absence of Hsp90 inhibitors. There was significant reduction in fluorescence compared to the level in the control, suggesting that E. histolytica Hsp90 is a selective target. The in vivo efficacy and safety of one Hsp90 inhibitor in a mouse model of amebic colitis and giardiasis was demonstrated by significant inhibition of parasite growth at a single oral dose of 5 mg/kg of body weight/day for 7 days and 10 mg/kg/day for 3 days. Considering the results for in vitro activity and in vivo efficacy, Hsp90 inhibitors represent a promising therapeutic option for amebiasis and giardiasis.
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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.