In vitro activity of pyrvinium pamoate against Entamoeba histolytica and Giardia intestinalis using radiolabelled thymidine incorporation and an SYBR Green I-based fluorescence assay

• Published in: Journal of antimicrobial chemotherapy Vol. 64; no. 4; pp. 751 - 754
• Main Authors: Downey, Autumn S., Graczyk, Thaddeus K., Sullivan, David J.
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.10.2009; Oxford Publishing Limited (England)
• Subjects: Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiprotozoal Agents - pharmacology; Biological and medical sciences; Clinical trials; Comparative studies; DNA - metabolism; DNA Replication - drug effects; drug; drug assay; Entamoeba histolytica; Entamoeba histolytica - drug effects; Gastroenterology; Giardia; Giardia intestinalis; Giardia lamblia - drug effects; Inhibitory Concentration 50; Medical sciences; Organic Chemicals - metabolism; Original Research; Parasites; Parasitic Sensitivity Tests - methods; Pharmacology; Pharmacology. Drug treatments; protozoan; Pyrvinium Compounds - pharmacology; Thymidine - metabolism; drug assay; protozoan; drug; Drug; Protozoa; Incorporation; Lobosea; Fluorescence; Entamoeba histolytica; Thymidine; In vitro; Biological activity; Pyrimidine nucleoside; Green
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dkp296

Objectives To assess the in vitro activity of the FDA-approved antihelminthic drug pyrvinium pamoate against Entamoeba histolytica and Giardia intestinalis. Methods A head-to-head comparison of a standard radiolabelled thymidine incorporation assay and the SYBR Green I-based fluorescence assay for determination of in vitro inhibition by pyrvinium and metronidazole was performed. Results The 50% inhibitory concentration (IC50) for treatment of E. histolytica with pyrvinium was 4–5 µM for both assays compared with 1–2 µM for metronidazole. For pyrvinium treatment of G. intestinalis, an IC50 of ∼12 µM was determined by the radiolabelled thymidine assay alone, with maximum inhibition around 60%. In contrast, the IC50 for metronidazole treatment using this assay was ∼2 µM. Conclusions Pyrvinium is a potential gut lumen agent for treatment of intestinal amoebiasis, but possibly not for giardiasis. SYBR Green I is an alternative screening method for E. histolytica, but not G. intestinalis.