Table 2. Inhibition of PfCRTCQR-Mediated CQ Transport in Oocytes, Intrinsic Antiplasmodial Activity, and in Vitro Resistance-Reversal Activity of Four CP Analogues.
| parasite growth relative to control (%)b |
CQ IC50 (nM) (RMI)c |
||||||
|---|---|---|---|---|---|---|---|
| compd | IC50 values (μM) for the inhibition of PfCRTCQRa | C2GC03 | C4Dd2 | C67G8 | C2GC03 | C4Dd2 | C67G8 |
| CQ | 14.5 ± 1.7 (1.00) | 154 ± 8 (1.00) | 110 ± 15 (1.00) | ||||
| VP | 33 ± 3 | 43 ± 6 | 46 ± 3 | 55 ± 5d | 13.1 ± 1.6 (0.91) | 36.2 ± 2.8 (0.23) | 71 ± 8 (0.65) |
| CP | 54 ± 5 | 97 ± 2 | 78 ± 5 | 76 ± 1d | 15.6 ± 1.7 (1.09) | 36.6 ± 0.7 (0.24) | 39.8 ± 3.1 (0.37) |
| 15c | 66 ± 8 | 99 ± 2 | 67 ± 3d | 72 ± 4d | 13.8 ± 1.8 (0.95) | 41 ± 2 (0.27) | 36.8 ± 1.9 (0.35) |
| 12a | 321 ± 24 | 100 ± 4 | 84 ± 5d | 90 ± 1 | 14.8 ± 2.4 (1.01) | 75 ± 2 (0.49) | 75 ± 5 (0.69) |
| 17c | 180 ± 29 | 100 ± 4 | 74 ± 5d | 79 ± 4d | 13.4 ± 1.9 (0.92) | 44 ± 2 (0.28) | 42 ± 3 (0.39) |
| 13c | 63 ± 7 | 99 ± 4 | 75 ± 2d | 74 ± 3d | 14.3 ± 1.6 (0.99) | 42 ± 4 (0.27) | 38.3 ± 4.1 (0.35) |
| PZ | 85 ± 7 | ||||||
| PQ | 68 ± 8 | ||||||
a
IC50 values (mean ± SEM) were determined from the data presented in Figure S1, Supporting Information. The IC50 value for VP is from Martin et al.5
b
Proliferation of pfcrt transfectant parasite lines in the presence of the test compound (800 nM), relative to the control.
c
IC50 of CQ (mean ± SEM) against the pfcrt transfectant lines in the presence of the test compound (800 nM), relative to the control. The response modification index (RMI) equals the IC50 of CQ determined in the presence of the compound/the IC50 of CQ measured in the absence of the compound.
d
Significantly different from C2GC03 (P < 0.05). [See Supporting Information for further details.]