Table 2. ABS P. falciparum (Dd2 strain) growth inhibition potencies of 1 and enantiopure benzo-ring substitution variantsa.
| Compound | X | Dd2 strain P. falciparum growth inhibition EC50 (nM) | % recoveryb (200 μM IPP) |
|---|---|---|---|
| 1 | H | 250 ± 70 nMc | 100%@2.5 μMc |
| 18a | 5-Br | >10 000 | nd |
| 18c | 7-Br | 4300 ± 600 | nd |
| 18d | 8-Br | >10 000 | nd |
| 19c | 7-Cl | 1300 ± 100 | nd |
| 20a | 5-F | 451 ± 28 | 100%@2.5 μM |
| 20b | 6-F | 1250–2500 | nd |
| 20c | 7-F | 501 ± 47 | 100%@2.5 μM |
| 20d | 8-F | 717 ± 73 | 100%@10 μM |
| 20e | 5,7-F2 | 964 ± 63 | 80%@10 μM |
| 21a | 5-CN | >10 000 | nd |
| 21b | 6-CN | >10 000 | nd |
| 21c | 7-CN | >20 000 | nd |
a
Growth inhibition (EC50 values) of ABS P. falciparum was determined using SYBR Green I assay at 72 h endpoint. Values represent average ± S.E.M from at least two biological replicates (with two technical replicates). P. falciparum Dd2 strain is multi-drug resistant. For compounds that did not achieve 100% growth inhibition at 10 000 nM, EC50 values are reported as “>X” where X is the highest concentration at which no inhibition was observed.
b
Recovery of parasite growth activity seen in the presence of 200 μM IPP, at the indicated concentration of drug.
c
Previously reported.8