Table 1.
Compd. | R1 | R2 | R3 | R4 | X | Cytotoxicity IC50 (μmol/L)a | Cytotoxicity of combination IC50 (μmol/L)b | Reversal foldc |
---|---|---|---|---|---|---|---|---|
PTX | – | – | – | – | – | 5.89 ± 0.24 | 5.89 ± 0.24 | 1 |
7a | OMe | OMe | OMe | O | >100 | 0.14 ± 0.01 | 43 | |
7b (NOB) | OMe | OMe | OMe | O | 44.67 ± 3.83 | 0.030 ± 0.002 | 185 | |
7c | OMe | OMe | OMe | O | 38.46 ± 3.30 | 0.080 ± 0.004 | 81 | |
13 | H | OMe | OMe | O | 74.99 ± 4.04 | 0.090 ± 0.005 | 66 | |
16 | Br | OMe | OMe | O | >100 | 0.15 ± 0.01 | 40 | |
18 | NH2 | OMe | OMe | O | 66.83 ± 3.99 | 0.29 ± 0.05 | 21 | |
23a | OMe | H | H | O | 66.83 ± 2.73 | 0.29 ± 0.01 | 21 | |
23b | OMe | H | H | O | 69.98 ± 6.78 | 0.44 ± 0.04 | 14 | |
23c | OMe | H | H | O | 39.36 ± 4.41 | 0.36 ± 0.02 | 17 | |
23d | OMe | OMe | H | O | 66.83 ± 2.73 | 0.13 ± 0.01 | 47 | |
28 | OMe | OMe | OMe | NH | >100 | 0.23 ± 0.02 | 27 | |
29a | OMe | OMe | OMe | NMe | 26.61 ± 2.63 | 0.11 ± 0.01 | 55 | |
29b | OMe | OMe | OMe | 21.13 ± 1.77 | 0.15 ± 0.01 | 40 | ||
29c | OMe | OMe | OMe | 59.57 ± 3.62 | 0.24 ± 0.01 | 26 | ||
29d | OMe | OMe | OMe | >100 | 0.070 ± 0.008 | 87 |
‒Not applicable.
Intrinsic cytotoxicity of target compounds or PTX alone to HCT8/T cells.
Values of IC50 for cytotoxicity of combination (P-gp inhibitor 10 μmol/L + PTX) were as mean ± SD of at least three independent experiments.
The reversal fold was calculated as a ratio of IC50 (PTX) to IC50 (P-gp inhibitor 10 μmol/L + PTX).