Table 2.
In vitro antimalarial activity (P. falciparum), cytotoxicity and MetHb formation activity of the N1-[4-(4-ethyl-6-methoxy-5-pentyloxy-8-quinolylamino)pentyl]-(2S/2R)-2-aminosubstitutedamides 51–63 (series 2).
| |||||||
|---|---|---|---|---|---|---|---|
| P. falciparum (D6 clone) | P. falciparum (W2 clone) | Vero cell cytotoxicity | MetHb toxicity | ||||
| S. No. | R | IC50 (ng/mL) | Sel. Index* | IC50 (ng/mL) | Sel. Index* | IC50 (ng/mL) | % MetHb formation (20 μg/mL) |
| 51 | (R)-Lys | 580 | >41.0 | 730 | >32.6 | NC | 48.7 |
| 52 | (R)-Orn | 700 | >34.0 | 1300 | >18.3 | NC | 43.6 |
| 53 | (S)-Arg | 1300 | >18.3 | 1400 | >3.4 | NC | 39.2 |
| 54 | (R)-Arg | 1400 | >17.0 | 1700 | >2.8 | NC | 46.1 |
| 55 | (S)-His | NA | – | NA | – | NC | NT |
| 56 | (R)-His | NA | – | NA | – | NC | NT |
| 57 | (S)-Trp | 860 | >20.9 | 950 | >18.9 | NC | 39.1 |
| 58 | (S)-Phe | 3700 | >6.4 | 2200 | >10.8 | NC | NT |
| 59 | (S)-Tyr | 3800 | >6.3 | 3300 | >7.2 | NC | NT |
| 60 | (S)-Met | 1900 | >12.5 | 1800 | >13.2 | NC | 34.2 |
| 61 | (S)-Ser | 4760 | >5.0 | 3600 | >6.6 | NC | NT |
| 62 | (R)-(Bzl)-Cys | 2000 | >11.9 | 1200 | >19.8 | NC | NT |
| 63 | (R)-Cys | NA | – | NA | – | NC | 47.5 |
| Primaquine (PQ) | 2000 | >11.9 | 2800 | >8.5 | NC | 47.9 | |
NC=not cytotoxic upto 23800 ng/mL (23.8 μg/mL)
NT = not tested
NA = Not active
Selectivity index is the ratio of IC50 in Vero cells to IC50 in P. falciparum (D6 or W2).
Chloroquine. IC50 = 14 ng/mL, Sel. Index = 1700 (D6 clone); IC50 = 100 ng/mL, Sel. Index = 238 (W6 clone).
Artemisinin. IC50 = 15.2 ng/mL, Sel. Index = 1565 (D6 clone); IC50 = 9 ng/mL, Sel. Index = 2644 (W6 clone).