Table 1.
Inhibitory effect of the synthesized compounds on proton channel function of wt or V27A mutant A/M2.a,b
| Compound | A/M2 wt (mean ± SE) | A/M2 V27A (mean ± SE) | ||
|---|---|---|---|---|
|
| ||||
| Inhibition by 100 μM for 2 min (%) | IC50 (μM) | Inhibition by 100 μM for 2 min (%) | IC50 (μM) | |
| Amantadine | 91.0 ± 2.1 | 16.0 ± 1.2 | 8.9 ± 1.0 | >50032 |
| 2 | 92.0 ± 1.4 | 4.1 ± 0.5 | 85.7 ± 1.5 | 3.6 ± 0.6 |
| 3 | 70.7 ± 2.4 | 45.3 ± 2.3 | 61.9 ± 2.3 | 60.6 ± 5.1 |
| 7 | 91.8 ± 1.0 | 1.9 ± 0.2 | 79.3 ± 2.8 | 16.2 ± 1.7 |
| 8 | 48.1 ± 3.4c | ND | 10.1 ± 0.6 | >500 |
| 11 | 10.9 ± 0.8d | ND | 13.1 ± 0.6 | ND |
| 13 | 43.9 ± 1.0 | ND | 23.5 ± 2.1 | ND |
| 15 | 18.4 ± 2.8 | ND | 14.6 ± 1.9 | ND |
| 16 | 64.0 ± 4.3 | ND | 44.2 ± 1.9 | ND |
| 17 | 76.7 ± 4.0 | ND | 47.3 ± 3.5 | ND |
| 18 | 48.9 ± 10.7 | ND | 29.2 ± 0.9 | ND |
| 19 | 89.9 ± 0.9 | 6.8 ± 1.4 | 63.0 ± 0.9 | 46.0 ± 1.1 |
| 20 | 94.7 ± 1.2 | 4.2 ± 0.1 | 77.8 ± 1.5 | 21.7 ± 2.6 |
a
The activity of the inhibitors was measured using the TEVC technique on A/M2 channels expressed in Xenopus oocytes; percentage of inhibition was the mean of at least three experiments. For IC50 experiments, 7–9 concentrations were measured, and, at each concentration, experiments were run at least three times.
b
Isochronic (2 min) values for IC50 are given.
c
The inhibition for 4 min was ca 75% and > 90% after 6 min of treatment.
d
The inhibition for 7 min was ca 25% and ca 30% after 10 min. See text and supporting information for details. ND, Not determined.