Table 1.
Inhibition screening of the selected ABMM compounds against ALDH1A1, ALDH1A3 and ALDH3A1. Enzyme activity was measured with hexanal (ALDH1A1 and ALDH1A3) or 4-NBA (ALDH3A1). Experimental values are shown as the mean ± standard error (SE). ND: Not Determined.
|
Remaining Activity ± SE (%) at 10 µM Compound | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| ALDH1A1 | ALDH1A3 | ALDH3A1 | |||||||
| R1 | R2 | R3 | X | Y | [S] at Saturation (30 µM Hex) |
[S] near Km (10 µM Hex) |
[S] at Saturation (250 µM Hex) |
[S] at Saturation (250 µM 4-NBA) |
|
| ABMM-1 | Cl | OCH3 | H | C=O | CHO | 81.93 ± 2.9 | 21.07 ± 0.1 | 61.14 ± 2.6 | ND |
| ABMM-2 | Cl | H | H | C=O | CHO | 56.98 ± 5.8 | 94.76 ± 8.3 | 79.70 ± 1.9 | 162.08 ± 10.7 |
| ABMM-5 | NO2 | OCH3 | H | C=O | CHO | 92.38 ± 4.6 | 61.93 ± 5.8 | 79.78 ± 5.9 | ND |
| ABMM-6 | F | OCH3 | H | C=O | CH=CHCHO | 94.76 ± 8.3 | 76.26 ± 3.5 | 91.27 ± 1.8 | 92.54 ± 11.4 |
| ABMM-15 | Cl | H | H | CH2 | CHO | 48.22 ± 2.8 | 0.14 ± 0.1 | 12.35 ± 0.7 | 146.35 ± 2.7 |
| ABMM-16 | Cl | OCH3 | H | CH2 | CHO | 42.27 ± 1.7 | 4.27 ± 1.8 | 19.22 ± 0.5 | 117.43 ± 3.5 |
| ABMM-17 * | Cl | H | --- | C=O | CHO | 57.85 ± 5.5 | 113.0 ± 0.5 | 95.06 ± 1.9 | 104.43 ± 2.4 |
| ABMM-18 | F | OCH3 | OCH3 | C=O | CHO | 70.86 ± 2.6 | 16.01 ± 3.4 | 77.30 ± 9.9 | 96.69 ± 3.3 |
| ABMM-19 | F | OCH3 | H | C=O | CH=CHCH2OH | 89.13 ± 0.4 | 88.32 ± 0.7 | 77.91 ± 7.4 | 124.32 ± 9.3 |
* Compound ABMM-17 has the oxygen at a position meta to Y; thus, no R3 group exists.