Table 3. Transport and Cell Association Studies of Amide/Thioamide Pair 17b and 18b with MDCK-MDR1 Cellsa and for Thiorhodamine Analogues 17a and 18a.
| compd | PAB, ×10–9 m s–1 | PBA, ×10–9 m s–1 | PBA/PAB | PPassive,b ×10–9 m s–1 | % cell associatedc | ratio (±inh)d |
|---|---|---|---|---|---|---|
| 17ae (+inh) | ≤1 | 230 ± 24 | 230 | 8.6 ± 0.1 | 5.2 | |
| ≤1 | 7.5 ± 0.1 | ∼4 | 45 ± 1 | |||
| 17b (+inh) | 0.9 ± 0.3 | 164 ± 4 | 182 | 16 ± 1 | 2.4 | |
| 1.0 ± 0.1 | 11.1 ± 0.2 | ∼6 | 39 ± 1 | |||
| 18ae (+inh) | ≤1 | 34 ± 22 | 34 | 34 ± 3 | 1.8 | |
| ≤1 | 0.2 ± 0.1 | <1 | 62 ± 1 | |||
| 18b (+inh) | 1.9 ± 0.5 | 29 ± 3 | 15 | 45 ± 1 | 1.2 | |
| 1.7 ± 0.2 | 1.8 ± 0.1 | ∼2 | 55 ± 1 |
a
Experiments were run with 5 μM dye and 4.3 mg mL–1 BSA. Values of transport in the absorptive (PAB) and secretory (PBA) mode in the absence or presence of inhibitor, the ratio PBA/PAB, the % cell associated rhodamine analogue in the absence or presence of inhibitor, and the ratio of cell associated rhodamine in the presence or absence of inhibitor are reported. Details for methods are provided in Experimental Section. Error limits are ± SD.
b
PPassive represents the mean of PAB and PBA in the fully inhibited system.
c
% cell associated is the fraction of mass extracted from the cell monolayer by methanol wash after a 1 h flux in the AB direction.
d
For % cell associated dye.
e
Values from ref (28).