Table 4.
The structure, physico-chemical properties, and antimalarial activitya of compounds 39–46.
| Compd. | Solubility (mg/L) | logP n-octanol/buffer |
P. berghei ED90 (mg/kg) |
P. berghei artesunate indexb |
P. yoelii ED90 (mg/kg) |
P. yoelii artesunate index | |||
|---|---|---|---|---|---|---|---|---|---|
| sc | po | sc | po | sc | po | sc | |||
| Artesunate | 565 | 2.77 | 7.2 | 7.1 | 1.0 | 1.0 | 22.0 | -- | 1.0 |
| 39 | 8 | 5.62 | 0.8 | 3.5 | 9.0 | 2.0 | 0.85 | 3.0 | 25.9 |
| 40 | < 2 | 4.78 | 0.6 | 2.8 | 12 | 2.5 | 0.52 | 2.0 | 42.3 |
| 41 | 89 | 2.49 | 1.5 | 3.1 | 4.8 | 2.3 | 3.9 | 5.0 | 5.6 |
| 42 | < 1 | 5.59 | 1.16 | 5.0 | 6.2 | 1.4 | 1.08 | -- | 20.4 |
| 43 | < 1 | 6.15 | 3.8 | 4.6 | 1.9 | 1.7 | 3.0 | -- | 7.3 |
| Artesunatec | 565 | 2.77 | 4.6 | 9.3 | 1.0 | 1.0 | 42.0 | -- | 1.0 |
| 44 | 28.4 | 3.05 | 0.18 | 1.3 | 25.6 | 7.15 | 1.25 | 1.84 | 33.6 |
| 45 | < 2 | 4.97 | 0.51 | 1.9 | 9.0 | 4.9 | 0.61 | 2.0 | 81.0 |
| Artesunatec | 565 | 2.77 | 12.0 | -- | 1.0 | -- | 50.0 | -- | 1.0 |
| 46 | 1251 | 2.63 | 9.0 | -- | 1.3 | -- | 10.0 | -- | 5.0 |
| Artemisinin | 63 | 2.94 | -- | -- | -- | -- | -- | -- | -- |
| Artemether | 117 | 3.98 | -- | -- | -- | -- | -- | -- | -- |
a
In vivo screens against CQ-sensitive P. berghei N strain and CQ-resistant P. yoelii NS strain. Peters׳ four-day test with mice treated daily subcutaneously (sc) or orally (po) from the day of infection (Day 0) through Day 3; results (ED90 values) were based on parasite counts in peripheral blood on day 4.
b
ED90 (artesunate) / ED90 (tested compound).
c
The variation in artesunate activity in different experiments.