Antitrypanosomal activities (μM ± standard deviation) of compounds against T. cruzi strain CL.
| Compd. | Anti-epimastigote activity | Anti-trypomastigote activity | ||||
|---|---|---|---|---|---|---|
| IC50 (μM) | SI5a | IC50 (μM) | SI6b | SI7c | SpI3d | |
| NFA | >10 | — | >10 | — | — | — |
| 1a | 7.66 ± 0.37 | 2 | 2.31 ± 0.11 | 7 | 42 | 3.32 |
| 2a | 3.56 ± 0.46 | 13 | 1.95 ± 0.09 | 24 | 51 | 3.32 |
| 3a | 2.41 ± 0.05 | 41 | 3.05 ± 0.06 | 33 | 33 | 0.79 |
| 4a | 46.15 ± 9.12 | 2 | >10 | — | — | — |
| 5a | 3.69 ± 0.60 | 27 | 4.04 ± 0.09 | 25 | 25 | 0.91 |
| 6a | 4.92 ± 0.47 | 10 | 6.14 ± 0.01 | 8 | 16 | 0.80 |
| 7a | 95.24 ± 4.03 | 1 | >10 | — | — | — |
| 8a | 7.30 ± 2.77 | 3 | 1.74 ± 0.01 | 11 | 27 | 4.20 |
| 9a | 2.63 ± 0.01 | 4 | 0.78 ± 0.01 | 15 | 21 | 3.37 |
| NTA | >10 | — | 1.62 ± 0.05 | 8 | 16 | — |
| 1b | 9.21 ± 1.03 | 5 | 2.50 ± 0.05 | 17 | 40 | 3.68 |
| 2b | >10 | — | 6.56 ± 0.22 | 15 | 15 | — |
| 8b | >10 | — | 3.04 ± 0.06 | 11 | 8 | — |
| 11 | >10 | — | >10 | |||
| 12 | >10 | — | >10 | |||
| NFZ | 7.83 ± 1.04 | 13 | 2.23 ± 0.06 | 45 | 45 | 3.51 |
| FZD | 2.01 ± 0.41 | 50 | 3.30 ± 0.25 | 30 | 30 | 0.61 |
| Bzn | — | — | 4.79 ± 0.56 | 21 | 21 | — |
SI5 = IC50 Vero/IC50 epimastigote.
SI6 = IC50 Vero/IC50 trypomastigote.
SI7 = IC50 THP-1/IC50 trypomastigote. Specificity index (SpI) < 0.4 indicates more anti-epimastigote activity, 0.4 < SpI < 2.0 indicates activity against both forms, SpI > 2.0 indicates more antitrypomastigote activity.55
Specificity index of T. cruzi: SpI3 = IC50 epimastigote/IC50 trypomastigote. Vero: African green monkey kidney epithelial cells; blue = compounds qualifying as antileishmanial/antitrypanosomal hits;52 red = compounds qualifying as potential antileishmanial leads.52 All data reported in the tables were significant at p < 0.05. NFA: 5-nitro-2-furaldehyde; NTA: 5-nitro-2-thiophenecarboxaldehyde; FZD: furazolidone; NFZ: nitrofurazone; Em: emetine; Bzn: benznidazole; AmB: amphotericin B; —: not determined; >10: compound did not qualify for IC50 determination due to low growth inhibition presented during single-point screening.