Table 1. In Vitro COXI and COXII Inhibition by the Three Mutual Prodrugsa.
| |
+ porcine liver esterase |
||||
|---|---|---|---|---|---|
| compd | CoxI | CoxII | CoxI | CoxII | SIb |
| IB–MP | no inhibition | 1.8 ± 0.2 (15%) | 4.7 ± 0.3 (100%) | 1.3 ± 0.15 (100%) | 3.6 |
| IB | 10.1 ± 1.2 (100%) | 4.3 ± 0.46 (100%) | |||
| DIC–MP | 7.1 ± 0.9 (29%) | no inhibition | 0.25 ± 0.03 (100%) | 9.9 ± 0.22 (100%) | 0.03 |
| DIC | 0.32 ± 0.03 (100%) | 16.9 ± 1.8 (100%) | |||
| KET–MP | 0.2 ± 0.01 (43%) | 0.04 ± 0.01 (19%) | 0.48 ± 0.06 (100%) | 2.2 ± 0.21 (100%) | 0.22 |
| KET | 0.8 ± 0.06 (100%) | 3.8 ± 0.8 (100%) | |||
| BET–MP | 24.0 ± 2 (43%) | no inhibition | 24.0 ± 2 (43%) | no inhibition | <0.1 |
a
Values represent IC50 (μM) and % inhibition at saturation.
b
In vitro COXII selectivity index (CoxI IC50/CoxII IC50) calculated in the presence of PLE.