Table 2.
Anti-HCV activities and cytotoxicity of analogues of 31 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 | ||
| 34 | >200 | 71 ± 6 | 29.2 ± 1.2 | >7 | 66 ± 10 | 12.3 ± 1.0 | >16 |
| 35 | 45.6 ± 6.1 | 81 ± 3 | 35.8 ± 3.4 | >1 | 96 ± 3 | 9.9 ± 1.6 | >5 |
| 36 | <25 | 92 ± 1 | ND | ND | 99 ± 1 | ND | ND |
| 37 | 155.6 ± 11 | 50 ± 8 | ND | ND | 83 ± 3 | 15.4 ± 3.9 | >10 |
| 38 | >200 | 37 ± 18 | ND | ND | 48 ± 11 | ND | ND |
| 39 | 80.8 ± 3.1 | 95 ± 4 | 7.9 ± 0.5 | 10 | 99 ± 1 | 2.6 ± 0.4 | 32 |
| 40 | >200 | 75 ± 7 | 15.0 ± 1.3 | 13 | 98 ± 2 | 7.3 ± 1.4 | 27 |
| 41 | 118.8 ± 2.8 | 35 ± 6 | ND | ND | 69 ± 2 | 32.1 ± 4.1 | 4 |
| 42 | 137.4 ± 1.0 | 99 ± 1 | 11.8 ± 0.6 | 12 | 96 ± 2 | 4.9 ± 0.3 | 28 |
| 43 | 48.9 ± 1.7 | 96 ± 2 | 9.2 ± 0.6 | 5 | 99 ± 1 | 6.5 ± 0.6 | 8 |
| 44 | 84.3 ± 1.3 | 74 ± 4 | 13.2 ± 1.4 | 6 | 95 ± 3 | 13.7 ± 2.1 | 6 |
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.