Interaction of apigenin-7-O-glucoside with pyrimethamine against Toxoplasma gondii growth
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Apigenin-7-O-glucoside, a flavonoid glucoside known to inhibit cancer cell growth, fungi growth, both intra and extracellular reactive oxygen species generation, causing cell arrest and damage to the plasma membrane, was tested alone or in combination with a dihydrofolate inhibitor (pyrimethamine) against Toxoplasma gondii (T. gondii) growth. The anti-T. gondii activity was carried out using a high throughput antiparasitic drug screening cell-based assay known as 2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H tetrazolium, monosodium salt (WST-8) and fluorescence plate reader. The 50% effective concentration inhibition and 95% confidence interval values for individual and combination treatments against T. gondii were 0.80 (0.38–1.29) µg/mL, 1.05 (0.275–2.029) µg/mL, and 0.40 (0–1.06) µg/mL for apigenin-7-O-glucoside, pyrimethamine, and apigenin-7-O-glucoside plus pyrimethamine, respectively. Interestingly, the apigenin-7-O-glucoside plus pyrimethamine combination showed an additive inhibition effect against T. gondii growth in vitro using the fractional inhibitory concentration index method. It was discovered that the apigenin-7-O-glucoside combination with pyrimethamine had a high selectivity index 62.5, which implies 62-fold inhibition activity against the parasite versus human foreskin fibroblast cell cytotoxicity. This new combination hit is novel and will have the potential for future effective, safe, and less costly anti-Toxoplasma drug development, if its in vivo activity shows similar findings.
KeywordsDrug combination Anti-toxoplasmosis Pyrimethamine Flavonoid glucoside
We are truly grateful to Professor Emeritus Adriane G. Ludwick for her constructive comments that have improved the manuscript. In addition, the authors are thankful for the support of the RCMI core facility at Tuskegee University that was established with Grant Number G12MD007585-23 for supporting the cell-based assay acquisition.
Both DAA and WHW conceived the present idea reported in this paper. DAA carried out the laboratory work, perform the Graph pad Prism analysis, and drafted the first manuscript. WHM provided the cell lines and proofread the whole manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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