Table 3.
Bisulfite adduct derivatives of GC373. GC376 and bisulfite adduct derivatives singly (2a, 2b) or doubly (2c—2f) modified at the P2 or P3 positions, or with variations in counter ion (3a, 3b) are shown, along with SARS-CoV-2 Mpro IC50 and SARS CoV-2 antiviral EC50 values, both with and without co-administration of efflux inhibitor CP-100356 (+CP). Cytotoxicity assays showed CC50 values of >200 μM for all compounds shown. ND indicates that value was not determined.
| Entry | Structure | IC50 (μM) | EC50 (μM) | EC50 (μM) +CP |
|---|---|---|---|---|
| GC376 [6] |  |
0.19 ± 0.04 | 0.9 ± 0.2 | 0.25 ± 0.02 |
| 2a |  |
0.08 ± 0.03 | 0.9 ± 0.3 | 0.27 ± 0.2 |
| 2b |  |
0.07 ± 0.02 | 1.7 ± 0.3 | 0.32 ± 0.04 |
| 2c |  |
0.07 ± 0.01 | 0.57 ± 0.07 | 0.19 ± 0.06 |
| 2d |  |
0.08 ± 0.02 | 0.7 ± 0.2 | 0.18 ± 0.04 |
| 2e |  |
0.04 ± 0.01 | 1.8 ± 0.4 | 0.29 ± 0.03 |
| 2f |  |
0.05 ± 0.03 | 1.2 ± 0.2 | 0.5 ± 0.1 |
| 3a |  |
0.20 ± 0.04 | 0.8 ± 0.3 | ND |
| 3b |  |
0.18 ± 0.04 | 1.2 ± 0.2 | ND |