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In vitro antagonistic and indifferent activity of combination of 3-deoxyanthocyanidins against Toxoplasma gondii

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Abstract

Toxoplasma gondii is a ubiquitous intracellular zoonotic parasite estimated to affect about 30–90% of the world’s human population. The most affected are immunocompromised individuals such as HIV-AIDS and cancer patients, organ and tissue transplant recipients, and congenitally infected children. No effective and safe drugs and vaccines are available against all forms of the parasite. We report here the antagonistic and indifferent activity of the combination of five different formulations of pure synthetic 3-deoxyanthocyaninidin (3-DA) chloride compounds against T. gondii tachyzoites and the synergistic and additive interaction against a human foreskin fibroblast (HFF) cell line in vitro using fluorescence microscopy, trypan blue assay, and fractional inhibitory concentration index. The individual and the combined pure 3-DA compounds were observed to have effective inhibition against T. gondii parasites with less cytotoxic effect in a ratio of 1:1. The IC50 values for parasite inhibition ranged from 1.88 μg/mL (1.51–2.32 μg/mL) for luteolinindin plus 7-methoxyapigeninindin (LU/7-MAP) and 2.23 μg/mL (1.66–2.97 μg/mL) for apigeninindin plus 7-methoxyapigeninindin (AP/7-MAP) combinations at 95% confidence interval (CI) after 48 h of culture. We found LU/7-MAP to be antagonistic and AP/7-MAP to be indifferent in interaction against T. gondii growth. Both individual and combination 3-DA compounds not only depicted very strong inhibitory activity against T. gondii, but also had synergistic and additive cytotoxic effects against HFF cells. These synthetic 3-DAs have potential as antiparasitic agents for the treatment of human toxoplasmosis.

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Acknowledgements

We are grateful to the Department of Chemistry, Tuskegee University, for their support. In addition, we wish to acknowledge the RCMI core lab team and grant number G12MD007585-23 for their support in the microscopy work. We thank Peak Serum for providing us with optimal original fetal bovine serum.

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Authors and Affiliations

  1. Department of Chemistry, College of Arts and Sciences, Laboratory of Ethnomedicine, Parasitology and Drug Discovery, Tuskegee University, Tuskegee, USA

    Daniel A. Abugri

  2. Department of Biology, College of Arts and Sciences, Tuskegee University, Tuskegee, AL, USA

    Daniel A. Abugri

  3. Department of Pathobiology, College of Veterinary Medicine, University of Illinois, Urbana-Champaign, 2001 South Lincoln Avenue, Urbana, IL, 61802, USA

    William H. Witola

  4. Department of Agricultural and Environmental Sciences, College of Agriculture, Environment and Nutrition Sciences, Tuskegee University, Tuskegee, AL, USA

    Jesse M. Jaynes

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  1. Daniel A. Abugri
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Correspondence to Daniel A. Abugri.

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Abugri, D.A., Witola, W.H. & Jaynes, J.M. In vitro antagonistic and indifferent activity of combination of 3-deoxyanthocyanidins against Toxoplasma gondii . Parasitol Res 116, 3387–3400 (2017). https://doi.org/10.1007/s00436-017-5661-1

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