Table 5.
Structure and cytotoxicity of benzothiazole PAC-1 derivatives.
| |||||||
|---|---|---|---|---|---|---|---|
| 72h IC50 (μM) | |||||||
| Compound | R1 | R2 | HT-29 | MDA-MB-231 | MKN-45 | NCI-H226 | SK-N-SH |
| 26a | NMe2 | 3-All | N.D. | 3.55 ± 0.17 | 1.01 ± 0.15 | N.D. | 1.68 ± 0.11 |
| 26b | NMe2 | 3,5-(t-Bu)2 | N.D. | 13.9 ± 0.24 | 2.48 ± 0.08 | N.D. | 2.28 ± 0.04 |
| 26c | NEt2 | 3-All | N.D. | 5.25 ± 0.19 | 1.80 ± 0.12 | N.D. | 2.10 ± 0.09 |
| 26d | NEt2 | 3,5-(t-Bu)2 | N.D. | 7.23 ± 1.01 | 4.06 ± 1.26 | N.D. | 2.46 ± 0.21 |
| 26e | 4-Me-1-Pip | 3-All | N.D. | 3.11 ± 0.31 | 1.31 ± 0.22 | N.D. | 2.58 ± 0.12 |
| 26f | 4-Me-1-Pip | 3,5-(t-Bu)2 | N.D. | 12.1 ± 0.15 | 9.70 ± 0.26 | N.D. | 2.79 ± 0.13 |
| 26g | NMe2 | 4-OBn | 2.19 ± 0.17 | 1.34 ± 0.11 | 1.06 ± 0.10 | 0.91 ± 0.03 | 1.14 ± 0.11 |
| 26h | NMe2 | 4-OCH2(4-F-Ph) | 1.32 ± 0.07 | 2.02 ± 0.01 | 1.72 ± 0.04 | 0.42 ± 0.05 | 0.88 ± 0.03 |
| 26i | NMe2 | 4-OCH2(3-F-Ph) | 1.03 ± 0.12 | 2.02 ± 0.12 | 1.35 ± 0.04 | 0.51 ± 0.03 | 1.29 ± 0.08 |
| 26j | NMe2 | 4-OCH2(2-F-Ph) | 1.51 ± 0.04 | 0.66 ± 0.02 | 0.35 ± 0.03 | 0.59 ± 0.01 | 1.94 ± 0.15 |
| 26k | NMe2 | 4-OCH2(4-CF3-Ph) | 0.92 ± 0.08 | 0.63 ± 0.03 | 0.29 ± 0.01 | 0.24 ± 0.02 | 0.60 ± 0.02 |
| 26l | NMe2 | 4-OCH2(2,4-Cl2-Ph) | N.D. | 2.02 ± 0.13 | 1.38 ± 0.05 | 0.50 ± 0.04 | 0.59 ± 0.01 |
| 26m | NMe2 | 4-OCH2(2,3-Cl2-Ph) | N.D. | 2.94 ± 0.08 | 1.45 ± 0.03 | 0.81 ± 0.01 | 0.87 ± 0.02 |
| 26n | NEt2 | 4-OCH2(4-F-Ph) | 1.47 ± 0.03 | 0.97 ± 0.08 | 0.31 ± 0.07 | 0.57 ± 0.07 | 0.71 ± 0.06 |
| 26o | NEt2 | 4-OCH2(3-F-Ph) | 0.76 ± 0.02 | 1.12 ± 0.11 | 0.63 ± 0.10 | 1.05 ± 0.03 | 1.34 ± 0.05 |
| 26p | NEt2 | 4-OCH2(2-F-Ph) | 1.06 ± 0.12 | 0.88 ± 0.02 | 0.55 ± 0.02 | 0.62 ± 0.06 | 0.91 ± 0.15 |
| 26q | NEt2 | 4-OCH2(4-CF3-Ph) | 1.59 ± 0.14 | 1.06 ± 0.05 | 0.57 ± 0.01 | 0.54 ± 0.04 | 0.85 ± 0.02 |
| 26r | NEt2 | 4-OCH2(2,3-Cl2-Ph) | 4.01 ± 0.27 | 1.74 ± 0.02 | 0.71 ± 0.05 | 0.95 ± 0.02 | 1.41 ± 0.13 |
| 26s | 4-Me-1-Pip | 4-OCH2(4-F-Ph) | 4.01 ± 0.18 | 2.37 ± 0.04 | 0.79 ± 0.12 | 0.31 ± 0.03 | 0.40 ± 0.01 |
| 26t | 4-Me-1-Pip | 4-OCH2(3-F-Ph) | 1.02 ± 0.11 | 0.83 ± 0.05 | 0.38 ± 0.01 | 0.36 ± 0.04 | 0.56 ± 0.09 |
| 26u | 4-Me-1-Pip | 4-OCH2(2-F-Ph) | 1.65 ± 0.13 | 0.42 ± 0.01 | 0.40 ± 0.02 | 0.45 ± 0.05 | 1.38 ± 0.11 |
| 26v | 4-Me-1-Pip | 4-OCH2(4-CF3-Ph) | 1.12 ± 0.06 | 0.58 ± 0.03 | 0.31 ± 0.02 | 0.65 ± 0.11 | 0.75 ± 0.08 |
| 26w | 4-Me-1-Pip | 4-OCH2(2,3-Cl2-Ph) | 3.34 ± 0.18 | 1.00 ± 0.11 | 0.45 ± 0.07 | 0.33 ± 0.05 | 0.55 ± 0.09 |
| 26x | NMe2 | - | N.D. | 16.18 ± 0.55 | 5.32 ± 0.12 | N.D. | 6.12 ± 1.12 |
| 26y | NEt2 | - | N.D. | 12.7 ± 0.36 | 5.83 ± 0.48 | N.D. | 4.37 ± 0.69 |
| 26z | 4-Me-1-Pip | - | N.D. | 10.49 ± 1.05 | 4.35 ± 1.08 | N.D. | 2.72 ± 0.15 |
| PAC-1 | - | - | 1.36 ± 0.02 | 4.58 ± 0.05 | 3.56 ± 0.05 | 1.02 ± 0.08 | 3.06 ± 0.16 |
Pip = piperidinyl; N.D. = not determined. [57]