Table 3.
In vitro activities of selected amino-artemisinins against liver stage P. berghei and cytotoxicitiesa.
| Compound | P. berghei sporozoites | Cytotoxicity EC50 | ||
|---|---|---|---|---|
| IC50 nM | Maximum inhibition % (Conc. μM) | HepG2 μM | SIb | |
| Atovaquone | 2.515 ± 0.997 | 94.85 ± 2.76 (0.5) | >0.25 | >100 |
| Puromycin | 22.7 ± 4.525 | 110 ± 4.24 (5) | 0.117 | 5.15 |
| Artemether 3 | >104 | 49.4 (10) | ND | ND |
| Artemiside 7 | 81.3 ± 9.616 | 99.05 ± 1.34 (5) | >25.0 | >308 |
| Artemisone 8 | 28.3 ± 01.273 | 93.35 ± 1.76 (10) | >50.0 | >1767 |
| DHA piperazine ureas | ||||
| 23 | 82.55 ± 4.172 | 104.75 ± 7.42 (10) | 5.45 | 66.0 |
| 24 | 105.5 ± 6.363 | 94.85 ± 2.76 (10) | 5.16 | 48.9 |
| DHA piperazine amides | ||||
| 27 | 168.0 ± 55.154 | 108 ± 4.24 (10) | 7.015 | 41.8 |
| 28 | 114.0 ± 15.556 | 104 ± 4.24 (10) | 8.32 | 73.0 |
a
Structures in Figures 1, 2 and Schemes 1, 2; luciferase-expressing P. berghei ANKA GFP-Luc-SMcon sporozoites were allowed to invade HepG2 cells and luciferase activity was measured after 48 h; data ± SD from biological duplicate and technical quadruplicate measurements.
b
SI = EC50 HepG2/IC50 P. berghei sporozoites. Assay was performed as previously described (Swann et al., 2016).