TABLE 1.
Activity of 1,2,4,5-tetraoxanes 1, 1,2,4,5,7,8-hexaoxonanes 2 and nonperoxidic isostere 3 against P. falciparum in vitro and P. berghei in vivo
| Compounda | IC50 (ng/ml)b K1/NF54 | Activity (%)c (p.o./s.c.) |
|---|---|---|
| 1a | 40/23 | 21/0 |
| 1b | 71/88 | 47/5 |
| 1c | 51/23 | 35/84 |
| 1d | 30/44 | 0/26 |
| 1e | 78/44 | 22/0 |
| 1f | 14/11 | 60/56 |
| 2a | 7400/5500 | ND |
| 2b | >10,000/>10,000 | ND |
| 2c | >10,000/>10,000 | ND |
| 2d | 770/2700 | ND |
| 2e | >10,000/>10,000 | ND |
| 2f | 2000/3200 | ND |
| 3 | >10,000/>10,000 | ND |
| WR 148999* | 7.2/10 | 99.7/>99.99 |
| Artemisinin* | 2.8/3.4 | 98/>99.99 |
a
*, Data from Dong et al. (6).
b
Mean from n = 2 to 3 determinations. Individual measurements differed by <50%.
c
Mean from n = 3 determinations. Individual measurements differed by <10%. ND, not determined. Data are presented as values for peroral (p.o.)/subcutaneous (s.c.) administrations.