Table 3.
Effect of PfCRT position 76 mutations on chemosensitization of quinine by T3.5 and verapamil in P. falciparum.
| Compound | IC50* (nM) P. falciparum | |||
|---|---|---|---|---|
| 106/1K76** | 106/176T*** | 106/176N*** | 106/176I*** | |
| Verapamil alone | 25800 ± 128 | 1779 ± 105 | 632 ± 78 | 8630 ± 312 |
| T3.5 alone | 93.6 ± 12 | 86.9 ± 8.5 | 134 ± 15 | 100.8 ± 18 |
| Chloroquine alone | 15.9 ± 1.4 | 188 ± 2.3 | 147 ± 6.8 | 158 ± 4.4 |
| Chloroquine + 500 nM verapamil | 17.2 ± 1.6 | 51.2 ± 3.2 | 39.9 ± 5.4 | 47.7 ± 5.6 |
| Chloroquine + 25 nM T3.5 | 14.5 ± 2.1 | 67.8 ± 9.8 | 74.3 ± 6.8 | 58.5 ± 6.1 |
| Quinine alone | 112 ± 18 | 204 ± 19 | 186 ± 21 | 20.8 ± 2.1 |
| Quinine + 500 nM verapamil | 118 ± 10 | 71.4 ± 8.9 | 53.5 ± 4.6 | 32.1 ± 2.4 |
| Quinine + 25 nM T3.5 | 55.6 ± 4.0 | 56.7 ± 5.3 | 71.2 ± 6.8 | 5.5 ± 0.8 |
Values are the means ± standard errors of the mean (S.E.M.) from three independent experiments, each in quadruplicate, utilizing the MSF assay with 0.2% parasitemia and 2% hematocrit.
Sudan 106/1K76 is known to have 7 of the 8 mutations in the pfcrt gene necessary for chloroquine resistance.
Mutant line selected with chloroquine pressure from 106/1K76.