Table 2.
Inhibitory activity of ligand-based series of compounds selected as potential cathepsin V inhibitors.
|
Cathepsin V |
Cathepsin L |
||||||
|---|---|---|---|---|---|---|---|
| Compound | Ri (%)a | Ki (µM)b | Ki′ (µM)b | Ri (%)a | Ki (µM)b | Ki′ (µM)b | |
| 28 |  |
1.1 ± 9.0 | −4.6 ± 5.2 | ||||
| 29 |  |
−0.5 ± 1.2 | −2.4 ± 2.0 | ||||
| 30 |  |
−2.0 ± 3.3 | −1.2 ± 0.3 | ||||
| 31 |  |
29.2 ± 7.0 | T.I.c | 20.9 ± 7.2 | T.I.c | ||
| 32 |  |
6.9 ± 2.2 | 4.7 ± 3.2 | ||||
| 33 |  |
−1.6 ± 6.5 | 3.4 ± 4.4 | ||||
| 34 |  |
14,0 ± 10.9 | −3.0 ± 0.5 | ||||
| 35 |  |
16.6 ± 8.4 | 12.0 ± 1.3 | ||||
| 36 |  |
15.2 ± 10.0 | −0.6 ± 1.7 | ||||
| 37 |  |
−3.4 ± 2.9 | −2.1 ± 0.7 | ||||
| 38 |  |
7.9 ± 0.4 | 2.3 ± 3.1 | ||||
| 39 |  |
17.1 ± 7.2 | 403.0 ± 79.7d | 6.1 ± 0.7 | 725.7 ± 142.3e | ||
| 40 |  |
27.6 ± 8.7 | 21.2 ± 2.0f | 12.4 ± 0.7 | 454.0 ± 69.1d | ||
| 41 |  |
17.7 ± 6.1 | 612.5 ± 23.9e | 4.2 ± 0.9 | n.i.g | ||
| 42 |  |
21.6 ± 4.6 | 155.8 ± 3.4e | 3.5 ± 3.1 | 319.2 ± 28.6e | ||
| 43 |  |
5.2 ± 1.8 | −0.4 ± 2.5 | ||||
| 44 |  |
11.1 ± 11.5 | 1.1 ± 4.9 | ||||
| 45 |  |
9.2 ± 6.4 | 3.3 ± 2.4 | ||||
| 46 |  |
12.1 ± 9.8 | 4.3 ± 4.1 | ||||
| 47 |  |
9.5 ± 2.5 | 4.4 ± 4.6 | ||||
| 48 |  |
20.4 ± 14.5 | 1187.2 ± 468.0d | 5.7 ± 3.6 | 1191.2 ± 357.4d | ||
| 49 |  |
22.9 ± 1.0 | 303.0 ± 11.3d | 12.9 ± 0.5 | 546.4 ± 114.4d | ||
| 50 |  |
−2.9 ± 4.0 | 13.8 ± 0.5 | ||||
| 51 |  |
−9.8 ± 5.8 | −4.0 ± 7.3 | ||||
| 52 |  |
0.3 ± 8.8 | −0.7 ± 1.5 | ||||
aRelative inhibition (Ri) determined at 50 μM, values are the mean ± SD (n = 2). b Ki and Ki′ values are the mean ± SD (n = 2). c T.I. – test interference, d Competitive inhibition, e Noncompetitive inhibition, f Uncompetitive inhibition, g n.i. – no inhibition.