Table 2. IC50 and EC50 values for hit compounds.
| SMDC # | IC50 (μM) & Maximum % Inhibitiona |
Pf EC50 (μM)b & % Inh @ 100 μM |
Cytox EC50 (μM) c & S.I. |
||||
|---|---|---|---|---|---|---|---|
| DPAP1 | DPAP3 | CatC | FP2 | FP3 | |||
| 153437A | 0.27 (0.02) 78 (1) |
25 (7) 100 (15) |
1.2 (1.5) 47 (8) |
~100 >60 |
2.3 (0.5) 100 (4) |
N.D. 28 (2) |
N.D. |
| 168313 | 1.8 (0.2) 78 (2) |
N.I. | ~100 >50 |
~50 >85 |
6.3 (0.5) 100 (7) |
N.D. 20 (1) |
N.D. |
| 31843PAIN | 2.2 (0.2) 71 (2) |
30 (8) 100 (14) |
~25 >75 |
~100 >70 |
5.7 (0.8) 100 (4) |
N.D. 24 (3) |
N.D. |
| 39848 | 34 (7) 94 (6) |
~100 >50 |
~100 >50 |
N.I. | N.I. | N.D. 13 (1) |
N.D. |
| 97214 | 7.2 (0.5) 100 (3) |
~100 >70 |
0.11 (0.01) 78 (1) |
0.25 (0.02) 96 (2) |
0.68 (0.08) 97 (3) |
N.D. 32 (4) |
N.D. |
| 158691 | 18 (8) 88 (12) |
N.I. | 9(3) 91 (9) |
1.00 (0.03) 100 (3) |
2.50 (0.04) 100 (4) |
9 (1) 88 (3) |
70 (8) 8 |
| 168314 | 200 (80) 100 |
~100 >50 |
N.I. | N.I. | N.I. | N.D. 35 (5) |
N.D. |
| 106517 | 5.7 (0.6) 67 (2) |
21 (3) 100 (8) |
~100 >50 |
~100 >80 |
7.2 (0.8) 100 (8) |
15 (3) 83 (5) |
160 (40) 11 |
| 106958 | 80 (50) 85 (2) |
~100 >50 |
~100 >50 |
~100 >80 |
6.5 (0.6) 100 (5) |
N.D. 25 (2) |
N.D. |
| 111619 | ~ 100 > 50 |
N.I. | ~50 >80 |
21 (5) 100 (7) |
18 (5) 100 (10) |
N.D. 35 (4) |
N.D. |
| 103222 | 1.7 (0.3) 51 (2) |
~50 >75 |
1.4 (0.3) 91 (4) |
20 (3) 36 (3) |
15.9 (0.8) 94 (1) |
23 (8) 75 (2) |
400 (120) 17 |
| 112370 | 0.6 (0.2) 42 (3) |
31 (6) 100 (10) |
13.5 (1.5) 64 (3) |
~50 >80 |
21 (3) 100 (6) |
N.D. 6 (1) |
N.D. |
| 112054 | 2.7 (0.1) 100 (1) |
>100 >35 |
0.9 (0.1) 100 (3) |
0.95 (0.02) 95 (2) |
0.52 (0.04) 100 (2) |
35 (5) 83 (9) |
350 (100) 10 |
a When we could not obtain a maximum inhibition baseline, an approximate IC50 value is given (~ sign) as the concentration where we observed 50% inhibition. The maximum level of inhibition obtained at the highest concentration is also reported (> sign).
b In vitro antiparasitic activity against P. falciparum was determined using a standard 72h replication assay (3 biological replicates).
c Cytotoxicity EC50 values were determined in human foreskin fibroblast cells using the CellTiter-Glo Assay from Promega (4 biological replicates). The specificity index (S.I.) was calculated by dividing the cytotoxicity EC50 value by the P. falciparum antiparasitic EC50 value.
PAIN Only one hit compound in which we performed follow-up study (SMDC31843) was identified as a PAIN molecule.
All experiments were performed in triplicate. Standard errors are shown in parentheses.
N.I. No inhibition. N.D. Not determined because treatment at 100 μM show no significant decrease in parasitemia.