ArticleAntimicrobial agents and chemotherapy2015
Azole Antifungal Agents To Treat the Human Pathogens Acanthamoeba castellanii and Acanthamoeba polyphaga through Inhibition of Sterol 14α-Demethylase (CYP51).
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Pooled it
- Article
- Amoebicidal and cysticidal in vitro activity of cationic dendritic molecules against Acanthamoeba polyphaga and Acanthamoeba griffini.Parasitology research · 2024Article
- Azole-based compounds as potential anti-RSC medicinal chemistry · 2024Article
- Identification of Potent and Selective Inhibitors ofJournal of medicinal chemistry · 2024Article
- Self-assembled micelles loaded with itraconazole as anti-Acanthamoeba nano-formulation.Archives of microbiology · 2024Article
- Druggable Sterol Metabolizing Enzymes in Infectious Diseases: Cell Targets to Therapeutic Leads.Biomolecules · 2024Review
- Infectious Keratitis in Patients Over 65: A Review on Treatment and Preserving Eyesight.Clinical interventions in aging · 2024Review
- Miconazole-like Scaffold is a Promising Lead forJournal of medicinal chemistry · 2023Article
- Domain-Swap Dimerization ofMolecular pharmacology · 2020Article
- In Vitro Effect of Pitavastatin and Its Synergistic Activity with Isavuconazole againstPathogens (Basel, Switzerland) · 2020Article
- Antiamoebic activity of synthetic tetrazoles against Acanthamoeba castellanii belonging to T4 genotype and effects of conjugation with silver nanoparticles.Parasitology research · 2020Article
- The Antifungal Drug Isavuconazole Is both Amebicidal and Cysticidal against Acanthamoeba castellanii.Antimicrobial agents and chemotherapy · 2020Article
- On the occurrence of cytochrome P450 in viruses.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Steroidal antibiotics are antimetabolites of Acanthamoeba steroidogenesis with phylogenetic implications.Journal of lipid research · 2019Article
- CYP51 as drug targets for fungi and protozoan parasites: past, present and future.Parasitology · 2018Review
- Microbial Sterolomics as a Chemical Biology Tool.Molecules (Basel, Switzerland) · 2018Review
- Functional importance for developmental regulation of sterol biosynthesis in Acanthamoeba castellanii.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2018Article
- Enzymatic chokepoints and synergistic drug targets in the sterol biosynthesis pathway of Naegleria fowleri.PLoS pathogens · 2018Article
- Sterol methyltransferase a target for anti-amoeba therapy: towards transition state analog and suicide substrate drug design.Journal of lipid research · 2017Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In this study, we investigate the amebicidal activities of the pharmaceutical triazole CYP51 inhibitors fluconazole, itraconazole, and voriconazole against Acanthamoeba castellanii and Acanthamoeba polyphaga and assess their potential as therapeutic agents against Acanthamoeba infections in humans. Amebicidal activities of the triazoles were assessed by in vitro minimum inhibition concentration (MIC) determinations using trophozoites of A. castellanii and A. polyphaga. In addition, triazole effectiveness was assessed by ligand binding studies and inhibition of CYP51 activity of purified A. castellanii CYP51 (AcCYP51) that was heterologously expressed in Escherichia coli. Itraconazole and voriconazole bound tightly to AcCYP51 (dissociation constant [Kd] of 10 and 13 nM), whereas fluconazole bound weakly (Kd of 2,137 nM). Both itraconazole and voriconazole were confirmed to be strong inhibitors of AcCYP51 activity (50% inhibitory concentrations [IC50] of 0.23 and 0.39 μM), whereas inhibition by fluconazole was weak (IC50, 30 μM). However, itraconazole was 8- to 16-fold less effective (MIC, 16 mg/liter) at inhibiting A. polyphaga and A. castellanii cell proliferation than voriconazole (MIC, 1 to 2 mg/liter), while fluconazole did not inhibit Acanthamoeba cell division (MIC, >64 mg/liter) in vitro. Voriconazole was an effective inhibitor of trophozoite proliferation for A. castellanii and A. polyphaga; therefore, it should be evaluated in trials versus itraconazole for controlling Acanthamoeba infections.
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