Table 4.
Compd | Mode of inhibiton | Inhibitor constants [μm] | IC50 [μm] | EC50 [μm] | |||
---|---|---|---|---|---|---|---|
Ki | Ki′ | TryR | hGR[b] | Parasite[c] | MRC-5[c] | ||
1 | linear mixed | 1.6±0.2 | 3.2±0.3 | 1.7 | >100 | 10.3 | >50 |
2 | NT[d] | – | – | 1.1 | NT | 6.0 | 18.7 |
3 | NT | – | – | 1.2 | NT | >50 | >50 |
4 | linear mixed | 3.0±0.2 | 4.3±0.3 | 4.2 | 74.2 | 25.6 | >50 |
5 | linear mixed | 2.0±0.1 | 3.0±0.2 | 4.7 | 33.4 | 18.7 | 31.1 |
6 | NT | – | – | 7.2 | NT | 6.9 | NT |
7 | NT | – | – | 5.1 | NT | 16.5 | NT |
10 | NT | – | – | 5.8 | NT | 19.2 | NT |
12 | NT | – | – | 14.4 | NT | 32.1 | 43.7 |
19 | NT | – | – | 8.4 | NT | 14.5 | NT |
39 | linear uncompetitive | 4.6±0.3 (T[S]2) 29.4±1.7 (NADPH) | – | 8.6 | >100 | 1.22 | 1.62 |
40 | linear uncompetitive | 3.0±0.2 (T[S]2) 21.5±1.6 (NADPH) | – | 12.8 | 10.0 | 1.43 | 3.2 |
41 | NT | – | – | 10.2 | NT | 8.1 | NT |
45 | NT | – | – | 13.0 | NT | 3.4 | 12.9 |
[a] MOI: Compounds 1–19 are from hit series 1 and 39–45 from hit series 2. [b] hGR: human glutathione reductase. [c] Concentration giving 50% growth inhibition after 73 h exposure. [d] NT: not tested.