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Toxoplasmosis is a prevalent disease affecting a wide range of hosts including approximately one-third of the human population. It is caused by the sporozoan parasite Toxoplasma gondii (T. gondii), which instigates a range of symptoms, manifesting as acute and chronic forms and varying from ocular to deleterious congenital or neuro-toxoplasmosis. Toxoplasmosis may cause serious health problems in fetuses, newborns, and immunocompromised patients. Recently, associations between toxoplasmosis and various neuropathies and different types of cancer were documented. In the veterinary sector, toxoplasmosis results in recurring abortions, leading to significant economic losses. Treatment of toxoplasmosis remains intricate and encompasses general antiparasitic and antibacterial drugs. The efficacy of these drugs is hindered by intolerance, side effects, and emergence of parasite resistance. Furthermore, all currently used drugs in the clinic target acute toxoplasmosis, with no or little effect on the chronic form.
Parasite Targets | ||||
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Apicoplast | Micronemes | Rhoptries | Mitochondria | Nucleus |
Inhibitors of Fatty Acid synthesis: -Clodinafop -Thiolactomycin -Triclosan |
BKI targeting TgCDPK1: -BKI-1294 -BKI-1294 analogs: Compounds 24 and 32) -BKI-1748 |
Oxindoles | Targeting HSP60 | Topo-isomerase 2 inhibitors: -Daunorubicin -Trovafloxacin -Enrofloxacin -Gatofloxacin |
Inhibitors of 2-Isoprenoid synthesis: -Fosmidomycin |
SP230 | 6-azaquinazolines | Atovaquone | Topo-isomerase 1 inhibitors: -Artemisinin -Artemisone -Artemiside -Artemether -Harmane -Harmine -Non-harmane |
Inhibitors of DNA gyrase: -Quinolones -Fuoroquinolones -Ciprofloxacin -Trovafloxacin -Ofloxacin -Temafloxacin |
Pyrazolopyridines | ELQ-271 | DNA-intercalating agents: -Fluphenasine -Thioridazine -Trifluoperazine -Hycanton -Phleomycin -Mitomycin C |
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Inhibitors of Protein synthesis: -Clindamycin -Spiramycin -Azithromycin |
Chemical scaffolds | ELQ-316 | Ribonucleotide reductase inhibitors: -Thiosemicarbazones -Hydroxyurea |
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Thiazolidinone derivatives | ELQ-400 | Oxidative DNA damage/DNA binding: -Resveratrol -Valproic acid |
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Naphtoquinones |