Table 3.
Enzymatic TgCDPK1 and Src inhibition (IC50), hERG inhibition (IC50), HepG2 and CRL-8155 growth inhibition (GI50) and T. gondii cellular assay (EC50) results for compounds with variable R1 and R2 substructures (20–37). IC50 and GI50 values are the averages of at least three assays. T. gondii cellular assay EC50 values are the average of at least two runs that were performed in triplicate.
| ||||||||
|---|---|---|---|---|---|---|---|---|
| R2 | R1 | IC50 (μM)
|
human cells, GI50 (μM)
|
EC50 (μM)
|
||||
| TgCDPK1 | Src | hERG | HepG2 | CRL-8155 | T. gondii | |||
|
1 |
|
0.0029 | >10 | 0.40 | >10 | >10 | 0.14 |
|
|
||||||||
|
20 |
|
0.0045 | >10 | 0.082 | >10 | >10 | 0.26 |
|
|
||||||||
|
21 |
|
0.00080 | >10 | >10 | >10 | >10 | 0.12 |
| 22 |
|
0.0011 | 3.7 | >10 | – | >10 | 0.071 | |
| 23 |
|
0.0012 | >10 | >10 | >10 | >10 | 0.090 | |
|
|
||||||||
|
24 |
|
0.0021 | >10 | 1.9 | >10 | >10 | 0.045 |
| 25 |
|
0.0018 | >10 | >10 | >10 | >10 | 0.21 | |
|
|
||||||||
|
26 |
|
0.0020 | >10 | >10 | >10 | >10 | 0.076 |
| 27 |
|
0.0020 | >10 | >10 | >10 | >10 | 0.078 | |
| 28 |
|
0.0024 | 0.37 | >10 | >10 | >10 | 0.077 | |
| 29 |
|
0.0018 | >10 | >10 | >10 | >10 | 0.081 | |
|
|
||||||||
|
30 |
|
0.0056 | >10 | – | >10 | >10 | 0.75 |
| 31 |
|
0.0033 | >10 | >10 | >10 | >10 | 0.17 | |
| 32 |
|
0.001 | >10 | >10 | >10 | >10 | 0.060 | |
| 33 |
|
0.002 | >10 | >10 | >10 | >10 | 0.16 | |
|
|
||||||||
|
34 |
|
0.00090 | 3.1 | >10 | >10 | >10 | 0.056 |
| 35 |
|
0.0013 | 7.4 | >10 | >10 | >10 | 0.018 | |
| 36 |
|
0.017 | >10 | – | >10 | >10 | 0.70 | |
|
|
||||||||
|
37 |
|
0.094 | >10 | – | >10 | >10 | – |
–Not tested