TABLE 1.
In vitro activity of amino artemisinins against asexual P. falciparum parasites
| Compound | Metabolic readout |
Proliferation readout |
Cytotoxicity |
|||||||
|---|---|---|---|---|---|---|---|---|---|---|
| IC50a (nM) |
RIb | IC50 (nM) |
RIc | IC50 (nM) W2 | RId | HepG2 cell viability (%)e | EC50 (μM) for CHO cells | |||
| NF54 | Dd2 | NF54 | K1 | |||||||
| CQ | 31.8 ± 9.9 | 119.0 ± 20.9 | 3.7 | 10 ± 3 | 154 ± 14 | 15.4 | 233 ± 49 | 23.3 | >55f (ref. 93) | NDg |
| MB | 0.3 ± 0.8 | 12.6 ± 4.0 | 43.3 | 5.0 ± 0.8 | 6.45 ± 0.30 | 1.29 | 5.13 ± 0.31 | 1.03 | ND | 52.6 ± 4.5 |
| Artemisinin | 10.8 ± 1.6 | 17.5 ± 2.5 | 1.6 | 0.57 ± 0.01 | 0.8 ± 0.5 | 1.40 | 0.37 ± 0.11 | 0.65 | ∼90 | ND |
| DHA | 0.8 ± 0.1 | 5.7 ± 2.0 | 7.1 | 2.51 ± 0.19 | 1.51 ± 0.33 | 0.60 | 1.74 ± 0.22 | 0.69 | ND | 25.2 ± 3.7 |
| Artesunate | 10.3 ± 0.8 | 40.5 ± 5.0 | 4.0 | 3.4 ± 0.7 | 4 ± 1 | 1.24 | 2.4 ± 0.4 | 0.72 | ∼90 | >354 |
| Artemether | 2.0 ± 0.1 | 17.3 ± 2.2 | 8.7 | 8 ± 1 | 9 ± 2 | 1.13 | 7 ± 1 | 0.86 | ∼90 | >335 |
| Artemisone | 3.0 ± 0.8 | 2.7 ± 0.3 | 0.9 | 1.2 ± 0.4 | 1.01 ± 0.19 | 0.85 | 1.6 ± 0.4 | 1.36 | ∼75 | >249 |
| Artemiside | 6.0 ± 1.8 | 8.2 ± 1.4 | 1.4 | 1.11 ± 0.17 | 1.6 ± 0.4 | 1.47 | 1.75 ± 0.27 | 1.58 | ∼80 | >271 |
| 10-Sulfamide | 10.9 ± 3.4 | 16.9 ± 2.6 | 1.55 | 3 ± 1 | 1.79 ± 0.26 | 0.56 | 2.04 ± 0.11 | 0.64 | ∼90 | 56.0 ± 4.6 |
| 10-Arylamine | 7.8 ± 1.9 | 11.1 ± 1.0 | 1.41 | 1.3 ± 0.6 | 0.64 ± 0.10 | 0.48 | 3 ± 1 | 2.55 | ∼90 | 2.9 ± 1.4 |
| 10-Piperazine | 3.2 ± 1.4 | 1.7 ± 0.2 | 0.5 | 3.1 ± 0.4 | 1.9 ± 0.5 | 0.61 | 1.4 ± 0.7 | 0.45 | ∼77 | ND |
| 10-Phenylurea | 1.3 ± 0.8 | 7.5 ± 0.4 | 5.8 | 4.7 ± 1.5 | 2.9 ± 0.6 | 0.61 | 1.7 ± 0.5 | 0.36 | ∼85 | 2.4 ± 1.0 |
The IC50s for asexual parasites were determined against drug-sensitive NF54 parasites or drug-resistant Dd2, K1, and W2 parasites using either a metabolic pLDH assay or a proliferative SYBR green I-based fluorescence assay. Data are means from at least three independent biological repeats performed in triplicate for both the metabolic and proliferative assays ± SEM and the mean from a single experiment performed in duplicate for cytotoxicity assays on the HepG2 and CHO cell lines ± SD.
Resistance index (RI) = IC50 for Dd2/IC50 for NF54.
Resistance index = IC50 for K1/IC50 for NF54.
Resistance index = IC50 for W2/IC50 for NF54.
Percent viability at 1,000× the IC50 against P. falciparum parasites.
The EC50 was 22 ± 0.4 μM (93).
ND, not determined.