TABLE 2.
Compounds without known modes of action against Toxoplasma gondiia
| Compound class and no. | Reference(s) | In vitro IC50 | Host cell TD50 | In vivo survivability | In vivo chronic infection | Parasite burden | In vivo toxicity |
|---|---|---|---|---|---|---|---|
| 3-[{2-((E)-furan-2-ylmethylene)hydrazinyl}methylene]-1,3-dihydroindol-2-one (ATT-5126) | 152 | ||||||
| Compound 47 | 19.7 μM | 35.4 µM HeLa cells | ND | ND | 10,000 RH strain tachyzoites injected i.p.; 19% reduction in tachyzoite burden in peritoneal cavity | ND | |
| 6-Trifluoromethyl-2-thiouracil (KH-0562) | 152 | ||||||
| Compound 48 | 32.2 μM | 56.3 μM HeLa cells | ND | ND | 10,000 RH strain tachyzoites injected i.p.; 24% reduction in tachyzoite burden in peritoneal cavity | ND | |
| Diamidines | 178, 179 | ||||||
| Compound 49 | 0.03 μM (179) | >2 μM HFF cells (179) | ND | ND | ND | ND | |
| Metal and metal complexes | 93, 180, 181 | ||||||
| Compound 50 | 0.0187 μM (180) | 2.4 μM HFF cells (180) | ND | ND | ND | ND | |
| Compound 51 | ND (93) | ND | ND | ND | 3,500 RH strain tachyzoites injected i.p.; group treated 4 days preinfection had ∼45%–50% reduced organ burdens; group treated 4 days postinfection had ∼86% reduced spleen burden (93) | >200 μg/ml (93) | |
| Compound 52 | 3.6 μM (181) | >200 μM LLC-MK2 cells (181) | ND | ND | ND | ND | |
| Resorcinarenes | 182 | ||||||
| Compound 53 | ND | 4,239 μM RAW 264.7 cells | ME49 strain, unspecified no. or life stage of parasites; led to 50% increase in survival in treatment group | 25 ME49 strain bradyzoites delivered orally; no reduction in brain cysts in treatment group | ND | >500 mg/kg | |
| Semisynthetic artemisinins | 90, 183–187 | ||||||
| Compound 54 | 108 μM (90) | ND | 1,000,000 PRU-Luc-GFP strain tachyzoites injected i.p.; 60% survival in treatment group (90) | (Coadministered with sulfadiazine until 23dpi) 1,000,000 PRU-Luc-GFP strain tachyzoites injected i.p.; significant reduction in brain cysts in treatment group (90) | ND | ND | |
| Compound 55 | ND (186) | ND | 50 RH strain tachyzoites injected i.p.; treatment increased survival by 6–7 days (186) | 18 ME49 strain bradyzoites injected i.p.; ∼40% reduction of cyst burden in treatment group (186) | ND | <10 mg/kg (186) | |
| Compound 56 | 0.25 μM | >320 μM HFF cells | ND | ND | ND | ND | |
| Aculeatins | 188 | ||||||
| Compound 57 | 0.173 μM | 0.173 μM K562 cells | ND | ND | ND | ND | |
| Clodinafop and derivatives | 189 | ||||||
| Compound 58 | 10 μM led to 70% growth inhibition; IC50 not established | >400 μM HFF cells | ND | ND | ND | ND | |
| Indirubin analogues | 174 | ||||||
| Compound 59 | 0.18 μM | 20 μM HFF cells | ND | ND | ND | ND | |
| Quinones (exptl) | 190, 191 | ||||||
| Compound 60 | 1.74 μM (191) | >6 μg/ml THP-1 cells (191) | ND | ND | ND | ND | |
| Compound 61 | 3.37 μM (191) | >6 μg/ml THP-1 cells (191) | ND | ND | ND | ND | |
| Compound 62 | 8.36 μM led to 96.5% growth inhibition; IC50 not established (190) | >2 μg/ml in THP-1 cells (190) | ND | ND | ND | ND | |
| Compound 63 | 8.73 μM led to 92% growth inhibition; IC50 not established (190) | >2 μg/ml in THP-1 cells (190) | ND | ND | ND | ND | |
| Thiazolidinones | 192 | ||||||
| Compound 64 | 0.9 μM | 35 μM HFF cells | ND | ND | ND | ND | |
| Thioureides | 193 | ||||||
| Compound 65 | 0.3 μM | No noted effect on HFF or Caco2 cells; exact numbers not reported | ND | ND | ND | ND | |
| Indole-1,2-diones | 194 | ||||||
| Compound 66 | 0.3 μM | 6.4 μM HFF cells | ND | ND | ND | ND |
Individual compound information is listed with the index number assigned to the specific molecule's structure. For cases in which multiple IC50 values were found in the literature, the lowest observed IC50 is reported. Anti-Toxoplasma compounds are grouped by structure. Structures for each compound can be found in Table S2 in the supplemental material. The in vivo survivability assay data refer to experiments where model organisms (mice) were exposed to a lethal infectious dose of parasite, often via i.p. injection. The strain and dose of the parasite and the recipient host differed between studies, making comparisons between studies problematic. In vivo chronic infection and parasite burden data refer to the tissue or fluid counts of parasites isolated from a host following a nonlethal infection or bradyzoite cyst burden in brain tissue (most often determined via PCR). ND, not determined; dpi, days postinfection; HFF, human foreskin fibroblasts.