Table 1. In vitro and in vivo antimalarial activity of the compounds.
|
In vitro activity against P. falciparum IC50, nM
|
In vivo activity against P. vinckei (rodent model)
|
|||||
|---|---|---|---|---|---|---|
| CQ-sensitive
|
CQ-resistant
|
|||||
| Compounds | Nigerian | 3D7 | FCB1 | FCM29 | ED50 i.p., mg/kg | ED50 p.o., mg/kg |
| T4 | 0.65 ± 0.15 | 1.3 ± 0.23 | 2.4 | 2.0 ± 0.3 | 0.14 ± 0.01 | ND |
| TE4gt (proT4) | 2.5 ± 0.21 | 7.0 | 3.2 | 4.5 | 3.4 | 90 |
| TE4a (proT4) | 1.1 ± 0.03 | 4.8 | 3.6 | 5.5 | 0.12 | 11 ± 0.77 |
| T3 | 3.0 ± 0.03 | 2.3 ± 0.75 | 6.3 | 4.7 ± 1.1 | 0.2 ± 0.02 | >10 |
| TE3 (proT3) | 2.25 ± 0.38 | 4.8 ± 1.62 | 3.2 | 5.7 | 0.25 | 5 ± 0.28 |
| TM1 | 3,533 ± 897 | 1,033 ± 484 | ND | ND | ND | ND |
| CQ | 20.0 ± 2.5 | 20.0 ± 1.6 | 160.0 | 400.0 ± 57 | 1.1 | 3.4 |
IC50 values were assessed after 48-hr contact of infected RBCs with the drug. ED50 values against P. vinckei were determined after i.p. administration of the compounds once daily for 4 days in infected mice, and parasitemia levels were determined on the day after the last administration. Values are the means of at least three independent experiments performed in triplicate (SEM is indicated). Otherwise, values are the means of two independent experiments (each performed in triplicate) differing by <15%. There was no recrudescence after 20 days at 4- to 5-fold ED50. ND, not determined; p.o., orally.