Table 1.
| ||||
---|---|---|---|---|
Entry | Compound | X | P. falciparum Dd2 straina IC50 (nM) | % Rescue (+ 200 μM IPP)b |
1 | FOS | 880 ± 70 | 100@ 10 μM | |
2 |
MMV 008138 |
2′,4′-Cl2 | 210 ± 90 | 100 @ 2.5 μM |
3 | 4a | 2′,4′-Cl2 | 250 ± 70 | 100 @ 2.5 μM |
4 | ent-4a | 2′,4′-Cl2 | >10,000 | ND |
5 | 4b | H | >10,000 | ND |
6 | 4c | 2′-Cl | 3,280 ± 990 | 60 @ 10 μM |
7 | 4d | 4′-Cl | 1,170 ± 60 | 50 @ 10 μM |
8 | 4e | 2′-Cl, 4′-Me | 410 ± 40 | 100 @ 2.5 μM |
9 | 4f | 2′-Me, 4′-Cl | 700 ± 90 | 100 @ 2.5 μM |
10 | 4g | 2′,4′-Me2 | 70% inhibition @ 10,000 | ND |
11 | 4h | 2′,4′-F2 | 780 ± 175 | 100 @ 5 μM |
12 | 4i | 2′,4′-(OMe)2 | >20,000 | ND |
13 | 4j | 2′,4′-(CF3)2 | >10,000 | ND |
14 | 4k | 3′,4′-(OMe)2 | >20,000 | ND |
15 | 5a | 2′,4′-Cl2 | >10,000 | ND |
16 | ent-5a | 2′,4′-Cl2 | 3,000 ± 200 | 60 @ 10 μM |
17 | 5b | H | >10,000 | ND |
18 | 5e | 2′-Cl, 4′-Me | >10,000 | ND |
19 | 5g | 2′,4′-Me2 | >10,000 | ND |
20 | 5h | 2′,4′-F2 | >20,000 | ND |
MRA-150, chloroquine-resistant (intermediate), pyrimethamine-resistant, mefloquine-resistant.
Drug at indicated concentration; nd signifies “not determined.”