Table 3.
In vitro inhibition of SmTGR and both human related disulfide reductases hGR and hTrxR.
| Compound |
|
IC50 (nM) SmTGR assay[a] |
IC50 (nM) hGR assay[b] |
IC50 (nM) hTrxR assays | |||
|---|---|---|---|---|---|---|---|
| Placenta wild type hTrxR | Sec498Cys TrxR | ||||||
| R1 | R2 | Trx assay[c] | DTNB assay[d] | DTNB assay[d] | |||
| 1 | – Me |
|
482 | 2 300 | 2 000 | 3 000 | 40 000 |
| 2 | – Me |
|
462 | 8 500 | 1 500 | 1 200 | 6 000 |
| 3 | – Me |
|
407 | > 25 000 | 2 000 | 2 000 | > 100 000 |
| 4 | – Me |
|
457 | 5 500 | 700 | 700 | > 100 000 |
| 5 | – Me |
|
784 | > 5 000 | 800 | 800 | > 100 000 |
| 6 | – Me |
|
166 | 600 | 3 000 | 1 500 | > 50 000 |
| 7 | – Me |
|
200 | 12 000 | 800 | 1 500 | > 50 000 |
| 8 | – CHF2 |
|
144 | 2 100 | 13 | 14 | 370 |
| 9 | – CHF2 |
|
46 | - | - | - | - |
| PAT[a] |
|
173 | - | - | - | - | |
[a]
The values were determined at pH 7 and 25°C in the presence of 100 μM NADPH, 3 mM DTNB. PAT (potassium antimonyl tartrate) is used as drug reference.
[b]
The values were determined at pH 6.9 and 25°C in the presence of 100 μM NADPH, 1 mM GSSG
[c]
The values were determined at pH 7.4 and 25°C in the presence of 100 μM NADPH and 20 μM hTrxC72S after 10 min preincubation.[30]
[d]
The values were determined at pH 7.4 and 25°C in the presence of 200 μM NADPH and 3 mM DTNB after 10 min preincubation.[30]