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. 2021 May 27;22(11):5705. doi: 10.3390/ijms22115705

Table 1.

The effect of selected therapeutic agents on T. gondii viability and the oxidant–antioxidant balance in the parasite and in the host in in vitro studies.

Models Compound IC50 /EC50 Results/Oxidant–Antioxidant Effect References
Human foreskin fibroblasts tert-butyl hydroperoxide IC50 = 100 ± 8 nM • ↑ T. gondii parasites death
• stable viability of the host cells
• ↓ peroxiredoxin activity
• changes in redox status of the parasites and destruction of their oxidant homeostasis
5-hydroxy-1,4-naphtoquinone (Juglon) IC50 = 148 ± 6 nM
Phenazine methyl sulfate IC50 = 406 ± 134 nM [57]
Vero cell line from kidney of African green monkey Extract of Azadirachta indica leaves Toxoplasma
elimination at
concentrations higher than 2 mg/mL
 ↑ disorganization and elimination of intracellular tachyzoites
• antioxidant effect on host cells
[114]
Extract of Melia azedarach leaves Toxoplasma
elimination at
concentrations higher than 0.5 mg/mL
• ↑ disorganization and elimination of intracellular tachyzoites
• antioxidant effect on host cells
[113]
Human foreskin fibroblasts 6-oximes of the tryptanthrin (6,12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) and its 8-bromoderivative ID50 range (0.003 ÷ 1.3) µM • anti-T. gondii activity
• no host cell cytotoxicity
• hepatoprotection of host cells
• activation of the ERK-Nrf2 pathway
• ↓ oxidative damage
[101,102,105]
6-hydrazones of the tryptanthrin and its 8-bromoderivative ID50 range (0.31 ÷ 12) µM
6-hydroxy derivatives of the tryptanthrin and 8-bromotryptanthrin ID50 range (0.002 ÷ 8.7) µM
Vero cell line from kidney of African green monkey entry 4 Extract of Psidium guajava (guava) EC50 = 4.94 ± 0.039 µg/mL • inhibition of T. gondii growth
• no host toxicity
• moderate antioxidant—inhibition of free radicals action in host cells
[110]
Human foreskin fibroblasts 1-thio-β-D-glucopyranosatotriethylphosphine gold-2,3,4,6-tetraacetate (Auranofin) IC50 = 0.28 nM • ↓ viability of T. gondii parasites
• inhibition of thioredoxin reductase activity
• ↓ resistance to oxidative damage
[55,93,94]
LLC-MK2 host cells—kidney epithelial cells of rhesus monkey [Fe(1-(bis-pyridin-2-ylmethyl-amino)-3-chloropropan-2-ol)(SO4)]2 µ-oxo IC50 = 3.6 µM nontoxic up to 200 µM • inhibition of parasites growth at concentration for 2.5–25 µM
• no effect on host cell viability
• ↑ oxidative stress
• ↓ metalloenzymes activity
[92]
Human foreskin fibroblasts Gold nanoparticles (AuNPs) EC50 ≤ 7 µg/mL • ↓ viability of the parasites
• no host toxicity
• alteration in redox status by ROS production and reduction in mitochondrial membrane potential
[97]
Silver nanoparticles (AgNPs) EC50 ≤ 1 µg/mL
Platinum nanoparticles (PtNPs) EC50 ≤ 100 µg/mL
Vero cell line from kidney of African green monkey Extract of Aloe vera IC50 = 13.2 µg/mL • anti-T. gondii activity in infected cells
• ↓ MDA levels in host cells
• potent antioxidant effect
[111]
Extract of Eucalyptus globulus IC50 = 24.7 µg/mL
Human foreskin fibroblasts Seed oil of the fruit of Cola gigantea EC50 ≤ 15 µg/mL • ↓ viability of T. gondii parasites
• ↑ toxicity for parasites by ROS production
• mild antioxidant potential in host cells
[112]
GES-1 cells Amide of 10-oxo derivative of ursolic acid and 1-H-tetrazol-5-amine IC50 = 218.6 µM reduction of number of T. gondii invading of host cells
• antioxidant effect on host cells
[115]

EC50, half maximal effective concentration.; ERK-Nrf2, extracellular signal-regulated kinase-Nuclear factor-E2 p45-related factor; GES-1 cells, human gastric epithelial cell line; IC50, half maximal inhibitory concentration; ID50, infective dose; MDA, malondialdehyde; ROS, reactive oxygen species. In column 4, the anti-T. gondii activities of the therapeutic agents are marked in blue, and their specific oxidant-antioxidant effects in black.