Table 1.
Screening data, inhibition constants and binding efficiency obtained for the selected compounds.
| Compound | MW (Da) | Screening (μM) | CpOGA IC50 (μM) | CpOGA Ki (μM) | hOGA IC50 (μM) | HexA/B IC50 (μM) | Selectivity (HexA/B/hOGA) | hOGA BEIa,b |
|---|---|---|---|---|---|---|---|---|
| Acetazolamide | 222 | 90 | 80 ± 14 | n.d. | 47.0 ± 0.1 | 32 ± 2 | 0.7 | 21 |
| Buspirone | 386 | 52 | 50 ± 15 | n.d. | 25.0 ± 0.1 | 47 ± 3 | 1.9 | 13 |
| Diprophylline | 254 | 79 | 60 ± 10 | 25 ± 2 | 121 ± 10 | 200 ± 30 | 1.6 | 16 |
| Ketoconazole | 531 | 38 | 2.0 ± 0.4 | 15 ± 5 | 4.3 ± 0.4 | 11 ± 1 | 2.6 | 11 |
| Semustine | 248 | 81 | 39 ± 6 | 23 ± 7 | 262 ± 6 | 2500 | 9 | 16 |
| N6-methyladenine | 149 | – | 21 ± 4 | 14 ± 1 | 4.0 ± 0.3 | 300 | 75 | 34 |
| Streptozotocin | 265 | 87 | 30c | n.d. | 1500d | 45 000 | 30 | 11 |
| NAG-thiazoline | 219 | – | – | n.d. | 0.07d | 0.07d | 1.0 | 32 |
| PUGNAc | 353 | – | – | 0.005e | 0.05d | 0.05d | 1.0 | 21 |
a
BEI Binding Efficiency Index (BEI) [46] calculated for hOGA inhibition, BEI = −log(Ki)/M,with M being the mass of the compound in kDa.
b
The Cheng–Prusoff equation (Ki = IC50/1 + ([S]/Km)) was used to convert the IC50 values to anabsolute inhibition constant (Ki).
c
Data taken from [31].
d
Ki value from [20].
e
Ki value from [24].