Table 3.
IC50 Values (μM) for 4, 7, and 9 against Microsomal CYP3A4, CYP1A2, and CYP2C9 under Dark and Light Conditionsa
| CYP3A4 | CYP1A2 | CYP2C9 | selectivity | |||||
|---|---|---|---|---|---|---|---|---|
| compd | dark | light | dark | light | dark | light | 1A2/3A4 dark (light) | 2C9/3A4 dark (light) |
| 4 | 0.183 ± 0.01 | 0.232 ± 0.018 | >100 | ND | 87 ± 2 | ND | 566 (ND) | 475 (ND) |
| 7 | 0.217 ± 0.011 | 0.301 ± 0.001 | 28 ± 2 | 23 ± 1 | 15 ± 3 | 18 ± 1 | 129 (76) | 69 (60) |
| 9 | 1.7 ± 0.1 | 1.6 ± 0.1 | >10 | >10 | >10 | >10 | >5.9 (>6.3) | >5.9 (>6.3) |
a
IC50 values determined using CYP3A4, CYP1A2, or CYP2C9 inhibitor screening kits (BioVision) following the manufacturer’s protocols. Stock solutions of 4, 7, or 9 were prepared in MeCN, plated, and combined with assay buffer and irradiated with a blue LED light source (tirr = 20 min, λirr = 460–470 nm, 56 J/cm2) or left in the dark. Experiments with compound 9 did not exceed 10 μM due to solubility limitations in assay buffer. Percent activities were determined vs vehicle control. IC50 values were determined using Igor Pro graphing software. Data are the average of three experiments, and errors are standard deviations.