Table 1.
Inhibitory potency of 3-substituted 2,4-PDCA derivatives against JMJD2E, PHD2 and formaldehyde dehydrogenase
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| Entry | Compound | Template | R | JMJD2E IC50/μMa |
JMJD2E Residual Activity (%)a |
PHD2 Residual Activity (%)b |
FDH Residual Activity (%)c |
| 1 | 5 | A | H | 0.44 | 0% | 22% | 100% |
| 2 | 33 | A | Br | n.d. | 67% | 100% | 100% |
| 3 | 34 | A | Ph | n.d. | 84% | 100% | 100% |
| 4 | 35 | A | (E)-CH=CHPh | 66 | 25% | 85% | 87% |
| 5 | 36 | A | OPh | n.d. | 48% | 88% | 91% |
| 6 | 37 | B | NHPh | 19 | 0% | 100% | 83% |
| 7 | 38 | B | NH-p-C6H4-OMe | 164 | 6% | 100% | 78% |
| 8 | 39 | B | NH-p-C6H4-NO2 | 95 | 0% | 100% | 100% |
| 9 | 40 | B | NH-p-C6H4-CO2H | 66 | 13% | 0% | 100% |
| 10 | 41 | B | NH-o,p-C6H3-diF | 48 | 12% | 100% | 100% |
| 11 | 42 | B | NH-o-C6H4-SMe | 48 | 5% | 100% | 80% |
| 12 | 43 | B | NH-o-C6H4-CO2H | 166 | 39% | 100% | 73% |
| 13 | 44 | B | NH-o-C6H4-NO2 | 56 | 6% | 100% | 59% |
| 14 | 45 | B | NH-o-C6H4-OMe | 19 | 2% | 100% | 76% |
| 15 | 46 | B | NH-o-C6H4-Me | 41 | 3% | 100% | 79% |
| 16 | 47 | B | NH-o-C6H4–F | 2.5 | d | 100% | d |
| 17 | 48 | A | NH-Naphthyl | 26 | 0% | 100% | 59% |
| 18 | 49 | A | NH-CH2-p-C6H4-OMe | 41 | 29% | 71% | 100% |
| 19 | 50 e | A | NH2 | 0.11 | d | 23% | d |
a
Determined by FDH-coupled assay; enzyme concentration 400 nM; residual activity reported at 200 μM compound concentration.
b
Determined by an HTRF-based assay; enzyme concentration 20 nM; residual activity reported at 400 μM compound concentration.
c
Enzyme concentration 50 μM; spectrophotometric assay; residual activity reported at 200 μM compound concentration.
d
Compound was fluorescent at the tested concentration.
e
Stock solutions prepared at 1 mM concentration because of limited solubility.