Table 1. In Vitro Antimalarial Activity and Cytotoxicity of 4-Aminoquinoline-pyrimidine Hybridsa.
|
P. falciparum (D6 clone) |
P. falciparum (W2 clone) |
IC50 (μM) |
|||||
|---|---|---|---|---|---|---|---|
| compd no. | IC50 (μM)b | SI | IC50 (μM) | SI | VERO | LLC-PK11 | HepG2 |
| 6a | 0.16 ± 0.05 | >3.70 × 102 | 0.5 ± 0.2 | >1.20 × 102 | NC | NC | NC |
| 6b | 0.33 ± 0.02 | >1.84 × 102 | 0.70 ± 0.04 | >85 | NC | NC | NC |
| 6c | 0.12 ± 0.03 | >5.00 × 102 | 0.68 ± 0.01 | >88 | NC | NC | NC |
| 6d | 0.44 ± 0.02 | 74.3 | 0.54 ± 0.00 | 60.6 | 32.7 ± 1.8 | 15.8 ± 1.0 | 9.1 ± 0.2 |
| 7a | 0.21 ± 0.06 | 2.05 × 102 | 0.81 ± 0.10 | 53.1 | 43.0 ± 0.0 | 42.3 ± 0.7 | 43.0 ± 0.0 |
| 7b | 0.24 ± 0.03 | >2.50 × 102 | 1.17 ± 0.07 | >51.3 | NC | NC | NC |
| 7c | 0.17 ± 0.02 | >3.53 × 102 | 0.64 ± 0.03 | >94 | NC | NC | 46.4 ± 6.6 |
| 7d | 0.14 ± 0.03 | 3.53 × 102 | 0.58 ± 0.01 | 85.2 | 49.4 ± 6.2 | 24.0 ± 0.6 | 8.1 ± 0.0 |
| 8a | ND | ND | ND | ND | ND | ND | ND |
| 8b | 0.02 ± 0.001 | >3.00 × 103 | 0.21 ± 0.003 | >2.85 × 102 | NC | NC | NC |
| 8c | 0.02 ± 0.002 | >3.00 × 103 | 0.09 ± 0.01 | >6.66 × 102 | NC | NC | NC |
| 8d | 0.06 ± 0.01 | 1.46 × 102 | 0.10 ± 0.02 | 88 | 8.8 ± 0.5 | 6.3 ± 0.4 | 6.4 ± 0.3 |
| 8e | 0.02 ± 0.002 | >3.00 × 103 | 0.14 ± 0.02 | >4.44 × 102 | NC | NC | NC |
| 8f | 0.02 ± 0.00 | >3.00 × 103 | 0.05 ± 0.004 | >1.20 × 103 | NC | 35.7 ± 0.6 | 26.2 ± 4.8 |
| 8g | ND | ND | ND | ND | ND | ND | ND |
| 8h | 0.03 ± 0.01 | 5.03 × 102 | 0.14 ± 0.02 | 1.07 × 102 | 15.1 ± 2.0 | 11.1 ± 1.3 | 6.4 ± 0.3 |
| 8i | 0.005 ± 0.001 | >1.20 × 104 | 0.03 ± 0.01 | >2.00 × 103 | NC | NC | NC |
| 8j | 0.007 ± 0.00 | >8.57 × 103 | 0.06 ± 0.002 | >1.00 × 103 | NC | 34.6 ± 0.6 | 26.7 ± 0.9 |
| 8k | 0.02 ± 0.001 | >3.00 × 103 | 0.02 ± 0.003 | >3.00 × 103 | NC | 34.6 ± 0.6 | 29.5 ± 2.3 |
| 8l | 0.007 ± 0.001 | 1.48 × 103 | 0.016 ± 0.001 | 6.50 × 102 | 10.4 ± 0.1 | 7.2 ± 0.2 | 6.3 ± 0.4 |
| 8m | 0.006 ± 0.00 | >1.00 × 104 | 0.06 ± 0.001 | >1.00 × 103 | NC | NC | NC |
| 8n | 0.02 ± 0.00 | 1.62 × 103 | 0.02 ± 0.003 | 1.62 × 103 | 32.4 ± 0.5 | 10.7 ± 0.2 | 15.4 ± 0.6 |
| CQ | 0.04 ± 0.004 | >1.50 × 103 | 0.39 ± 0.04 | >1.52 × 102 | NC | NC | NC |
| artemisinin | 0.01 ± 0.001 | >6.00 × 103 | 0.01 ± 0.00 | >6.00 × 103 | NC | NC | NC |
| pyrimethamine | 0.01 ± 0.003 | 1.82 × 103 | NA | 18.2 ± 0.1 | NT | NT | |
| doxorubicin | 8.6 ± 0.4 | 1.05 ± 0.05 | 1.0 ± 0.0 | ||||
a
IC50, the concentration that causes 50% growth inhibition; SI, selectivity index (IC50 for cytotoxicity to Vero cells/IC50 for antimalarial activity); and ND, not determined.
b
Average values of two independent experiments ± standard deviations (SDs). NA, not active up to highest tested concentration (19 μM). NC, no cytotoxicity up to 60 μM; NT, not tested; Vero, monkey kidney fibroblasts; LLC-PK11, pig kidney epithelial cells; and HepG2, human hepatoma cells.