Table 1. Enzyme Inhibition and Parasite Viability of Compound 1a.
| compd | R | R1 | PfDHODH IC50 (μM) | HsDHODH IC50 (μM) | 3D7 IC50 (μM) | Dd2 IC50 (μM) | LC50 (μM)b |
|---|---|---|---|---|---|---|---|
| 1a | H | H | >30 | na | >40 | >30 | na |
| 1b | H | Me | 1.08 | >30 | 0.28 | 0.42 | >62 |
| 1c | H | Et | 0.14 | >30 | 0.10 | 0.15 | >62 |
| 1d | H | n-Pr | 0.70 | >30 | 0.47 | 1.10 | >62 |
| 1e | H | i-Pr | 0.68 | >30 | 0.56 | 0.81 | >62 |
| 1f | H | c-Pr | 0.06 | >30 | 0.08 | 0.09 | >62 |
| 1g | H | c-Bu | 0.42 | >30 | 0.41 | 0.44 | >62 |
| 1h | H | n-Bu | 28.6 | >30 | >20 | 7.30 | na |
| 1i | H | c-Pentyl | 2.51 | >30 | 4.40 | 5.50 | na |
| 1j | H | diMe | >30 | na | >40 | >40 | na |
| 1k | Me | c-Pr | 0.08 (n = 3) | >30 | 0.09 (n = 3) | 0.11 (n = 3) | >62 |
| 1l | Et | c-Pr | 0.11 | >30 | 0.12 | 0.18 | >62 |
| 1m | n-Pr | c-Pr | 0.18 | 15.1 | 0.39 | 0.63 | >62 |
| 1n | OH | c-Pr | >30 | na | >5 | >5 | na |
| 1o | CF3 | c-Pr | 0.57 | >30 | 0.83 | 1.71 | >62 |
| 1p | NMe2 | c-Pr | 5.6 | na | >1 | >1 | >62 |
a
Assay conditions reported in ref (10).
b
LC50 is the lethal concentration required to kill 50% of human renal proximal tubule cells.