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  • Ascorbic acid potentiates the Giardia duodenalis growth inhibitory activity of pure Terminalia ferdinandiana Exell compounds

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    Accepted Manuscript (AM)
    Author(s)
    Cock, IE
    Rayan, P
    Griffith University Author(s)
    Cock, Ian E.
    Year published
    2020
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    Abstract
    Giardiasis, one of the most common causes of diarrhoeal disease, is caused by gastrointestinal protozoal parasites of the genus Giardia. Metronidazole is the most commonly used drug to treat giardiasis. However, metronidazole resistance is increasingly common, making the development of new anti-giardial drugs a high priority. A panel of 11 compounds previously identified in T. ferdinandiana fruit extracts were investigated for the ability to inhibit G. duodenalis proliferation. Eight of the 11 compounds inhibited the growth of all three G. duodenalis strains. 2,3-Dihydroxyphenyl B-D-glucopyranosiduronic acid (DPGA) was the ...
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    Giardiasis, one of the most common causes of diarrhoeal disease, is caused by gastrointestinal protozoal parasites of the genus Giardia. Metronidazole is the most commonly used drug to treat giardiasis. However, metronidazole resistance is increasingly common, making the development of new anti-giardial drugs a high priority. A panel of 11 compounds previously identified in T. ferdinandiana fruit extracts were investigated for the ability to inhibit G. duodenalis proliferation. Eight of the 11 compounds inhibited the growth of all three G. duodenalis strains. 2,3-Dihydroxyphenyl B-D-glucopyranosiduronic acid (DPGA) was the most potent anti-giardial compound, with IC50 values as low as 126 μM (38 μg/mL). Notably, DPGA inhibited a metronidazole-resistant G. duodenalis strain with similar activity as determined for the metronidazole-sensitive strains. Furthermore, the activity of DPGA was greatly potentiated when it was tested in combination with ascorbic acid, to approximately 17 μM (5 μg/mL) for the metronidazole-sensitive G. duodenalis strains and 40 μM (12 mg/mL) for the resistant strain. The T. ferdinandiana tannins (gallic acid and chebulic acid) were moderate inhibitors of G. duodenalis growth when tested in combination with ascorbic acid, although they had only low levels of activity when tested alone. All of the tested compounds (and their combinations with ascorbic acid) displayed low toxic effects and all compounds are conformed to Lipinski’s rules of 5 with few violations, indicating their potential as drug leads and chemotherapies for the treatment and prevention of giardiasis.
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    Journal Title
    Parasitology Research
    Volume
    119
    Issue
    3
    DOI
    https://doi.org/10.1007/s00436-019-06579-1
    Copyright Statement
    © 2020 Springer Berlin / Heidelberg. This is an electronic version of an article published in Parasitology Research, 2020, 119 (3), pp. 1125-1137. Parasitology Research is available online at: http://link.springer.com/ with the open URL of your article.
    Subject
    Microbiology
    Veterinary sciences
    Medical microbiology
    Science & Technology
    Life Sciences & Biomedicine
    Parasitology
    Gastrointestinal parasite
    Combinational therapies
    Publication URI
    http://hdl.handle.net/10072/395009
    Collection
    • Journal articles

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