Table 3.
Evaluation of a subset of oxine derivatives: selectivity against other cell lines and in vivo (HUVEC) activity on MetAPs and SIRT1
| IC50,a μM; 3H-T Uptake |
IC50,a μM; Calcein-AM |
IC50,a μM; hMetAPs |
Immunoblotb |
||||||
|---|---|---|---|---|---|---|---|---|---|
| Entry | HUVECc | HeLa | Jurkat-T | HUVEC | HFF | hMetAP1c | hMetAP2c | Ac-p53 | Met-14-3-3γ |
| 17 | 1.46 | ND | ND | ND | ND | >15 | >15 | + | − |
| 18 | 1.92 | ND | ND | 3.55 ± 0.9 | 3.66 ± 0.7 (b = 18%) | 14 | 0.33 | ND | ND |
| 24 | 0.324 | ND | ND | 0.746 ± 0.19 | 2.69 ± 0.5 (b = 17%) | >15 | 0.024 | ND | ND |
| 32 | 0.308 | 1.12 ± 0.2 | 0.79 ± 0.08 | 1.47 ± 0.2 | 0.909 ± 0.12 (b = 21%) | 6.97 | >15 | − | − |
| 5 | 1.90 | 3.97 ± 0.9 | 1.58 ± 0.3 | 5.13 ± 1.2 | 3.69 ± 1.0 (b = 21%) | >15 | 0.055 | ++ | + |
| 33 | 0.364 | 0.64 ± 0.2 | 0.36 ± 0.07 | 3.72 ± 0.8 | 9.08 ± 1.2 (b = 17%) | >15 | >50 | + | − |
| 34 | 0.218 | 2.36 ± 0.5 | 1.28 ± 0.3 | 1.84d ± 0.15 (b = 19%) | 37.3 ± 2.1 (b = 38%) | 8.92 | 11.88d | − | − |
| 40 | 0.789 | ND | ND | ND | ND | 6.45d | >40 | +++ | + |
| 45 | 0.273 | ND | ND | ND | ND | >40 | >15 | − | − |
| 46 | 1.6 | ND | ND | ND | ND | >15 | 0.434 | ++ | + |
| 47 | 2.01 | ND | ND | ND | ND | >15 | 0.117 | ++ | + |
| 48 | 0.77 | 2.41 ± 0.8 | 1.73 ± 0.2 | 4.21 ± 1.4 | 2.26 ± 0.3 (b = 23%) | >15 | 0.057 | +++ | + |
| 51 | 0.721 | ND | ND | 3.51 ± 1.1 | 4.77 ± 1.0 (b = 21%) | >40 | >15 | − | − |
| 54 | 0.204 | 0.59 ± 0.1 | 0.45 ± 0.05 | 1.32 ± 0.2 | 0.782 ± 0.13 (b = 22%) | 10.51 | >15 | − | + |
| 55 | 0.305 | 1.03 ± 0.2 | 0.82 ± 0.15 | 1.46 ± 0.21 | 0.783 ± 0.11 (b = 21%) | 21.05d | >15 | − | − |
Note: IC50 values are the average of at least three independent experiments, each one consisting of triplicates, and ± standard deviation is given.
Immunoblotting of compound treated HUVEC lysates (see Fig. 1): The inducers of p53 acetylation are grouped into four categories (−, +, ++, and +++) based on the immunoblot signals of negative control (DMSO, 1.0) and the positive control (nitroxoline at 5 μM, 11.6), thus −, <2.0; +, 2.0–7.0; ++, 7.1–11.6; +++, >11.6. In the case of Met-14-3-3γ the compounds are grouped into two categories (− and +) based on the immunoblot signals relative to the control (DMSO, 1.0), hence, −, >1.5; and +, ≥1.5.
Dose-response curve was non-sigmoidal; b = bottom value of the curve.