Table 6.
Plm I, II, IV inhibition and P. falciparum growth inhibition activity of selected compounds.
| Comp. | IC50 Plm I, μΜ |
IC50 Plm II, μΜ |
IC50 Plm IV, μΜ |
Sa | EC50b Pf Growth, nΜ |
|---|---|---|---|---|---|
| (S,R)-2a | 0.8 | 0.16 | 0.014 | 17.9 | 1.5 |
| (S,R)-3a | 7.4 | 5.4 | 0.048 | 43.8 | 2.0 |
| (S,R)-3b | 1.8 | 0.5 | 0.030 | 25.3 | 1.8 |
| (S,R)-3d | 2.5 | 2.2 | 0.024 | 24.2 | 2.0 |
| (S,R)-3h | 2.0 | 0.85 | 0.027 | 14.8 | 6.0 |
| (S,R)-4b | 3.1 | 1.7 | 0.058 | 19.8 | 0.3 |
| (S,R)-4c | 1.1 | 1.1 | 0.050 | 20 | 1.5 |
| (S,R)-4g | 0.78 | 0.27 | 0.018 | 38.9 | 6.0 |
| (S,R)-5a | 5.6 | 7.1 | 0.076 | 50.0 | 2.0 |
| (S,R)-5b | 10.3 | 10.4 | 0.15 | 32.6 | 6.0 |
a
Selectivity factor of Plm IV/Cat D inhibition.
b
The EC50 values for P. falciparum growth were determined using a SYBR Green-based assay with an incubation time of 96 h (2 erythrocytic cycles). Samples were each measured in triplicate, in 2 separate biological assays. Compound TCMDC-13467411,20 was used as a positive control (see Supporting Information).