TABLE 1.
In vitro activities, toxicities, and SIs of the Se derivatives for extra- and intracellular forms of Leishmania infantum
| Compound | IC50a (μM) for: |
SId |
|||
|---|---|---|---|---|---|
|
In vitro activityb |
Macrophage toxicityc | Promastigote forms | Amastigote forms | ||
| Promastigote forms | Amastigote forms | ||||
| Meglumine antimonate | 18.0 ± 3.1 | 24.2 ± 2.6 | 15.2 ± 1.0 | 0.8 | 0.6 |
| 1 | 44.1 ± 5.2 | 31.7 ± 2.0 | 92.6 ± 5.1 | 2 (3) | 3 (5) |
| 2 | 38.7 ± 2.9 | 23.8 ± 2.0 | 5.9 ± 0.6 | 0 (0) | 0 (0) |
| 3 | 36.5 ± 2.7 | 17.9 ± 1.4 | 61.5 ± 3.5 | 2 (2) | 3 (6) |
| 4 | 41.8 ± 4.1 | 16.9 ± 0.9 | 24.7 ± 2.2 | 0 (0) | 1 (2) |
| 5 | 23.9 ± 1.7 | 18.6 ± 1.7 | 19.6 ± 1.7 | 0 (0) | 1 (2) |
| 6 | 19.4 ± 1.6 | 10.4 ± 0.6 | 29.7 ± 2.6 | 1 (2) | 3 (5) |
| 7 | 35.9 ± 3.5 | 28.9 ± 2.2 | 44.8 ± 3.0 | 1 (1) | 2 (3) |
| 8 | 0.7 ± 0.2 | 3.7 ± 0.6 | 132.8 ± 7.5 | 190 (237) | 36 (60) |
| 9 | 13.8 ± 0.9 | 8.3 ± 0.4 | 51.3 ± 4.1 | 4 (5) | 6 (10) |
| 10 | 2.1 ± 0.5 | 4.6 ± 1.0 | 139.9 ± 8.3 | 67 (83) | 30 (51) |
| 11 | 1.9 ± 0.3 | 3.8 ± 0.7 | 62.9 ± 4.4 | 33 (41) | 17 (28) |
| 12 | 23.8 ± 1.1 | 16.4 ± 1.3 | 8.2 ± 0.7 | 0 (0) | 0 (0) |
| 13 | 3.5 ± 0.6 | 6.1 ± 0.3 | 10.1 ± 0.9 | 3 (4) | 1.6 (3) |
| 14 | 28.5 ± 1.9 | 14.8 ± 0.9 | 9.5 ± 1.1 | 0 (0) | 1 (1) |
| 15 | 0.8 ± 0.1 | 2.7 ± 0.3 | 49.4 ± 3.5 | 62 (77) | 18 (30) |
| 16 | 23.7 ± 2.6 | 11.7 ± 0.8 | 19.2 ± 0.7 | 0 (0) | 2 (3) |
| 17 | 16.7 ± 0.8 | 10.3 ± 0.7 | 19.3 ± 1.2 | 1 (1) | 2 (3) |
| 18 | 3.6 ± 0.7 | 5.5 ± 0.6 | 14.7 ± 1.2 | 4 (5) | 2.6 (4) |
| 19 | 41.9 ± 2.5 | 18.7 ± 1.3 | 70.0 ± 4.7 | 2 (2) | 4 (6) |
| 20 | 2.7 ± 0.8 | 3.7 ± 0.4 | 29.5 ± 2.4 | 11 (14) | 8 (13) |
| 21 | 1.2 ± 0.2 | 0.9 ± 0.0 | 8.3 ± 0.4 | 7 (9) | 9 (14) |
| 22 | 37.8 ± 2.5 | 17.5 ± 1.2 | 27.4 ± 0.9 | 0 (0) | 2 (3) |
| 23 | 47.0 ± 5.3 | 19.1 ± 1.6 | 60.3 ± 4.7 | 1 (1) | 3 (5) |
| 24 | 6.5 ± 0.7 | 3.6 ± 0.5 | 11.8 ± 0.8 | 2 (2) | 3.3 (5) |
| 25 | 18.4 ± 0.5 | 14.8 ± 0.7 | 72.4 ± 5.5 | 4 (5) | 5 (8) |
| 26 | 6.6 ± 0.4 | 4.1 ± 0.7 | 47.9 ± 3.1 | 7 (9) | 11.7 (19) |
| 27 | 28.6 ± 2.5 | 20.5 ± 1.7 | 112.3 ± 7.3 | 4 (5) | 11 (18) |
| 28 | 83.6 ± 6.8 | 37.8 ± 2.4 | 74.2 ± 6.6 | 0 (0) | 2 (3) |
| 29 | 7.1 ± 0.8 | 4.2 ± 1.0 | 22.7 ± 1.6 | 3 (4) | 5.4 (9) |
| 30 | 26.7 ± 2.0 | 18.7 ± 1.1 | 64.0 ± 3.0 | 2 (3) | 3 (6) |
| 31 | 16.8 ± 1.2 | 16.8 ± 0.9 | 185.9 ± 81.6 | 11 (14) | 11 (18) |
| 32 | 16.5 ± 2.0 | 13.3 ± 0.8 | 44.6 ± 2.4 | 3 (3) | 3 (6) |
| 33 | 7.9 ± 0.6 | 4.9 ± 0.8 | 44.1 ± 3.7 | 6 (7) | 9.0 (15) |
| 34 | 19.7 ± 1.2 | 15.2 ± 1.1 | 34.8 ± 2.4 | 2 (2) | 2 (4) |
| 35 | 3.9 ± 0.7 | 4.3 ± 0.6 | 41.8 ± 2.7 | 11 (13) | 10 (16) |
| 36 | 23.3 ± 1.7 | 21.6 ± 1.3 | 59.3 ± 3.7 | 2 (3) | 3 (5) |
| 37 | 4.8 ± 1.2 | 2.6 ± 0.2 | 17.3 ± 0.7 | 4 (4) | 6.6 (11) |
| 38 | 13.6 ± 0.8 | 8.9 ± 0.4 | 78.4 ± 5.7 | 6 (7) | 9 (15) |
| 39 | 36.5 ± 3.4 | 30.0 ± 2.2 | 50.7 ± 3.8 | 1 (2) | 2 (3) |
| 40 | 25.8 ± 2.7 | 17.7 ± 1.4 | 36.2 ± 2.4 | 1 (2) | 2 (3) |
| 41 | 19.0 ± 1.1 | 21.8 ± 1.2 | 9.6 ± 1.3 | 0 (0) | 0 (1) |
| 42 | 2.5 ± 0.6 | 3.2 ± 0.3 | 18.7 ± 0.6 | 7 (9) | 5.8 (10) |
| 43 | 8.9 ± 0.7 | 5.8 ± 1.1 | 28.5 ± 3.8 | 3 (4) | 4.9 (8) |
| 44 | 4.4 ± 0.3 | 3.9 ± 0.6 | 33.4 ± 3.0 | 8 (9) | 8.6 (14) |
| 45 | 3.7 ± 0.5 | 2.7 ± 0.3 | 61.1 ± 4.1 | 16 (21) | 23 (38) |
| 46 | 8.6 ± 0.8 | 6.3 ± 1.3 | 29.7 ± 1.8 | 3 (4) | 4.7 (8) |
| 47 | 1.1 ± 0.5 | 2.7 ± 0.5 | 12.6 ± 0.8 | 11 (14) | 5 (8) |
| 48 | 1.6 ± 0.1 | 1.4 ± 0.2 | 52.8 ± 3.61 | 33 (41) | 38 (63) |
a
Results are the averages from four separate determinations.
b
IC50, the concentration required to give 50% inhibition, calculated by linear regression analysis from the values of the equilibrium constants (Kc) at the concentrations employed (1, 10, 25, and 200 μM).
c
Toxicity against J774.2 macrophages after 72 h of culture.
d
SI, selectivity index, which is calculated as the IC50 for macrophage toxicity/IC50 for activity against the extracellular or intracellular form of the parasite. The number of times that the SI of the compound exceeded the SI of the reference drug is provided in parentheses.