ArticleScientific reports2017
Characterisation of sterol biosynthesis and validation of 14α-demethylase as a drug target in Acanthamoeba.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 41 citations in OpenAlex.
- Benzophenone Derivatives as a New Class of Anti-Infectives Against Acanthamoeba spp.Archiv der Pharmazie · 2026Article
- Metagenomic identification of Acanthamoeba Rhysodes in chronic skin lesion: Case report and literature review.JAAD case reports · 2026Article
- Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024Article
- Induction of Programmed Cell Death inAntioxidants (Basel, Switzerland) · 2023Article
- Statins Induce Actin Cytoskeleton Disassembly and an Apoptosis-Like Process inAntibiotics (Basel, Switzerland) · 2022Article
- Acanthamoeba Keratitis: A Single-Institution Series of Four Cases With Literature Review.Cureus · 2022Article
- The transcriptome of Balamuthia mandrillaris trophozoites for structure-guided drug design.Scientific reports · 2021Article
- Drug discovery for primary amebic meningoencephalitis: from screen to identification of leads.Expert review of anti-infective therapy · 2021Article
- Antifungal Activities ofMolecules (Basel, Switzerland) · 2021Article
- Evaluating Alternate Methods of Determining the Antimicrobial Efficacy of Contact Lens Care Products against Acanthamoeba Trophozoites.Pathogens (Basel, Switzerland) · 2021Article
- An Integrated Approach to Identify New Anti-Filarial Leads to Treat River Blindness, a Neglected Tropical Disease.Pathogens (Basel, Switzerland) · 2021Article
- Joining forces: Leveraging novel combination therapies to combat infections with eukaryotic pathogens.PLoS pathogens · 2020Article
- Domain-Swap Dimerization ofMolecular pharmacology · 2020Article
- Discovery of repurposing drug candidates for the treatment of diseases caused by pathogenic free-living amoebae.PLoS neglected tropical diseases · 2020Article
- In Vitro Effect of Pitavastatin and Its Synergistic Activity with Isavuconazole againstPathogens (Basel, Switzerland) · 2020Article
- Antiamoebic activity of 3-aryl-6,7-dimethoxyquinazolin-4(3H)-one library against Acanthamoeba castellanii.Parasitology research · 2020Article
- Drug Discovery againstPathogens (Basel, Switzerland) · 2020Review
- The Antifungal Drug Isavuconazole Is both Amebicidal and Cysticidal against Acanthamoeba castellanii.Antimicrobial agents and chemotherapy · 2020Article
- Disruption of the NF-κB/IL-8 Signaling Axis by Sulconazole Inhibits Human Breast Cancer Stem Cell Formation.Cells · 2019Article
- More than 18,000 effectors in theProceedings of the National Academy of Sciences of the United States of America · 2019Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The soil amoebae Acanthamoeba causes Acanthamoeba keratitis, a severe sight-threatening infection of the eye and the almost universally fatal granulomatous amoebic encephalitis. More effective treatments are required. Sterol biosynthesis has been effectively targeted in numerous fungi using azole compounds that inhibit the cytochrome P450 enzyme sterol 14α-demethylase. Herein, using Gas Chromatography Mass Spectrometry (GCMS), we demonstrate that the major sterol of Acanthamoeba castellanii is ergosterol and identify novel putative precursors and intermediate sterols in its production. Unlike previously reported, we find no evidence of 7-dehydrostigmasterol or any other phytosterol in Acanthamoeba. Of five azoles tested, we demonstrate that tioconazole and voriconazole have the greatest overall inhibition for all isolates of Acanthamoeba castellanii and Acanthamoeba polyphaga tested. While miconazole and sulconazole have intermediate activity econazole is least effective. Through GCMS, we demonstrate that voriconazole inhibits 14α-demethylase as treatment inhibits the production of ergosterol, but results in the accumulation of the lanosterol substrate. These data provide the most complete description of sterol metabolism in Acanthamoeba, provide a putative framework for their further study and validate 14α-demethylase as the target for azoles in Acanthamoeba.
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