TABLE 3.
Activities of novel structure-guided inhibitors of PMs on PM-KO lines
| Parasite line | IC50a |
||||||
|---|---|---|---|---|---|---|---|
| 11b (μM) | 13 (μM) | 15 (μM) | 19 (μM) | GB-III-24 (nM) | GB-III-28 (nM) | GB-III-32 (nM) | |
| Dd2 | 4.4 ± 0.2 | 3.2 ± 0.4 | 5.6 ± 1.1 | 7.3 ± 1.9 | 787.5 ± 41.7 | 824.7 ± 72.7 | 19.8 ± 2.1 |
| Δpfpm1 | 5.3 ± 0.7 | 2.9 ± 0.9 | 4.4 ± 0.6 | 8.3 ± 1.4 | 918.5 ± 80.3 | 1,074 ± 150.6 | 20.8 ± 3.2 |
| Δpfpm2 | 4.3 ± 0.2 | 3.8 ± 0.4 | 3.0 ± 0.6 | 3.3 ± 1.5 | 831.8 ± 77.0 | 892.5 ± 48.5 | 14.2 ± 3.7 |
| Δpfpm3 | 4.5 ± 0.2 | 3.4 ± 0.5 | 5.6 ± 0.9 | 5.5 ± 1.0 | 705.5 ± 39.9 | 615.4 ± 102.5 | 10.3 ± 1.7 |
| Δpfpm4 | 4.7 ± 0.4 | 3.2 ± 0.3 | 3.2 ± 0.3 | 7.2 ± 1.2 | 879.9 ± 146.1 | 874.1 ± 105.0 | 31.3 ± 4.7* |
| GC03 | 3.3 ± 0.5 | 1.7 ± 0.5 | 2.4 ± 0.5* | 10.1 ± 2.0 | 853.4 ± 27.8 | 796.0 ± 50.4 | 15.1 ± 2.4 |
| 3D7 | 4.2 ± 0.2 | 2.9 ± 0.3 | 6.2 ± 0.5 | 5.0 ± 0.4 | 1,364 ± 41.4 | 1,094 ± 77.1 | 19.9 ± 2.6 |
| Δ3pfpm | 4.3 ± 0.3 | 3.3 ± 0.5 | 5.7 ± 0.4 | 5.0 ± 0.4 | 1,240 ± 87.4 | 1,095 ± 91.8 | 14.6 ± 1.3 |
| Δ4pfpm | 3.8 ± 0.4 | 2.4 ± 0.2 | 6.0 ± 0.7 | 4.2 ± 0.5 | 1,088 ± 109.7 | 776.6 ± 86.5* | 15.3 ± 0.8 |
| PM V-mRFP | ND | ND | ND | ND | 1,706 ± 100.6 | 1,588 ± 76.0 | 27.6 ± 2.1 |
| PM X-mRFP | ND | ND | ND | ND | 1,477 ± 117.3 | 1,125 ± 145.4 | 72.5 ± 2.2*** |
a
IC50s are expressed as means ± SEMs. Each value was determined from three to six separate drug assays performed in duplicate. The degree of statistical significance in comparison to the result for the parental line (Dd2 for the single PM-KO lines and 3D7 for the triple and quadruple KO lines) is indicated with an asterisk(s): *, P < 0.05; ***, P < 0.001. ND, not determined.