Table 1.
Anti-HCV activities and cytotoxicity of the first 33 EDASA Scientific compounds evaluated on gt 1b and 2a.
| Cpd | CC50a (µM) | Huh7/Rep-Feo1b
|
Huh7.5-FGR-JC1-Rluc2A
|
||||
|---|---|---|---|---|---|---|---|
| Inhibition,b % | EC50c (µM) | SId | Inhibition,b % | EC50c (µM) | SId | ||
| 1 | >200 | 19 ± 6 | ND | ND | 80 ± 5 | 11.1 ± 0.9 | >18 |
| 2 | >200 | 22 ± 9 | ND | ND | 51 ± 8 | 48.5 ± 3.9 | >4 |
| 3 | >200 | NI | ND | ND | 49 ± 6 | ND | ND |
| 4 | >200 | NI | ND | ND | 36 ± 10 | ND | ND |
| 5 | >200 | 49 ± 12 | ND | ND | 66 ± 7 | 23.6 ± 4.0 | >8 |
| 6 | ND | 26 ± 1 | ND | ND | 54 ± 4 | ND | ND |
| 7 | >200 | NI | ND | ND | 78 ± 3 | 11.7 ± 0.9 | >17 |
| 8 | >200 | 21 ± 2 | ND | ND | 77 ± 7 | 14.1 ± 1.9 | >14 |
| 9 | >200 | 19 ± 10 | ND | ND | 72 ± 3 | 15.6 ± 3.7 | >13 |
| 10 | >200 | 21 ± 2 | ND | ND | 77 ± 7 | 17.3 ± 3.2 | >12 |
| 11 | >200 | NI | ND | ND | 67 ± 5 | 21.1 ± 4.4 | >9 |
| 12 | >200 | 19 ± 8 | ND | ND | NI | ND | ND |
| 13 | >200 | NI | ND | ND | 14 ± 8 | ND | ND |
| 14 | 85.6 ± 5.9 | 17 ± 3 | ND | ND | 65 ± 5 | 20.6 ± 2.9 | 4 |
| 15 | <25 | 88 ± 2 | ND | ND | 99 ± 1 | ND | ND |
| 16 | >200 | 39 ± 4 | ND | ND | 60 ± 6 | 22.5 ± 3.8 | >9 |
| 17 | >200 | NI | ND | ND | 62 ± 1 | 28.1 ± 4.8 | >7 |
| 18 | >200 | NI | ND | ND | 55 ± 9 | ND | ND |
| 19 | >200 | NI | ND | ND | 46 ± 8 | ND | ND |
| 20 | >200 | 54 ± 8 | ND | ND | 29 ± 8 | ND | ND |
| 21 | <25 | 92 ± 1 | ND | ND | 99 ± 1 | ND | ND |
| 22 | >200 | NI | ND | ND | 44 ± 9 | ND | ND |
| 23 | >200 | 45 ± 6 | ND | ND | 61 ± 9 | 24.8 ± 4.5 | >8 |
| 24 | >200 | 19 ± 9 | ND | ND | 85 ± 9 | 7.3 ± 0.5 | >27 |
| 25 | >200 | NI | ND | ND | 73 ± 3 | 4.9 ± 0.4 | >41 |
| 26 | >200 | NI | ND | ND | 76 ± 7 | 17.4 ± 0.8 | >11 |
| 27 | >200 | NI | ND | ND | 43 ± 10 | ND | ND |
| 28 | 114.7 ± 14.6 | 73 ± 9 | 24.3 ± 1.2 | 5 | 98 ± 2 | 6.0 ± 1.0 | >19 |
| 29 | >200 | NI | ND | ND | NI | ND | ND |
| 30 | >200 | NI | ND | ND | 28 ± 4 | ND | ND |
| 31 | 109.9 ± 2.9 | 66 ± 9 | 12.4 ± 1.0 | 9 | 88 ± 8 | 8.7 ± 1.9 | 13 |
| 32 | >200 | 50 ± 4 | ND | ND | 25 ± 5 | ND | ND |
| 33 | >200 | 45 ± 2 | ND | ND | 48 ± 11 | ND | ND |
CC50 values were determined in Huh7.5 parental cells by the MTS assay. CC50 = is the concentration required to reduce the bioreduction of MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxy-phenyl)-2-(4-sulfophenyl)-2H-tetrazolium) into formazan by 50%. The reported value represents the means ± SD of data derived from three independent experiments.
Anti-HCV activity of the compounds were carried out at 50 µM in preliminary screening.
The inhibition data from 8 to 12 quarter log dilutions were used to generate the dose response curves. EC50 = the effective concentration required to inhibit virus induced cytopathic effect by 50%. The reported values represent the means ± SD of data derived from three independent experiments.
SI: selectivity index ratio of CC50 to EC50. ND: not determined. NI: no inhibition.