Table 1.
IC50’s for sACE-1 inhibition by metal-chelate-lisinopril complexes, metal chelates, chelator-lisinopril compounds, and chelators.
| complex | IC50 (nM) | TD conc. (nM)a |
|---|---|---|
| [NTA]2-–lisinopril | 210 ± 40 | --b |
| [Fe-NTA]1+–lisinopril | 54 ± 9 | 7.8 |
| [Co-NTA]0–lisinopril | 45 ± 8 | 4.8 |
| [Ni-NTA]0–lisinopril | 44 ± 4 | 4.8 |
| [Cu-NTA]0–lisinopril | 90 ± 10 | 15 |
| [GGH]1+–lisinopril | 50 ± 10 | --b |
| [Co-GGH]0–lisinopril | 90 ± 10 | 20 |
| [Ni-GGH]0–lisinopril | 150 ± 30 | 25 |
| [Cu-GGH]0–lisinopril | 1,470 ± 20 | 300 |
| [EDTA]3-–lisinopril | 1,100 ± 100 | --b |
| [Fe-EDTA]0–lisinopril | 88 ± 5 | 14 |
| [Co-EDTA]1-–lisinopril | 1,200 ± 40 | 210 |
| [Ni-EDTA]1-–lisinopril | 1,420 ± 50 | 250 |
| [Cu-EDTA]1-–lisinopril | 960 ± 60 | 230 |
| [DOTA]3-–lisinopril | 6,800 ± 900 | --b |
| [Fe-DOTA]0–lisinopril | 3,800 ± 400 | 870 |
| [Co-DOTA]1-–lisinopril | 4,100 ± 200 | 790 |
| [Ni-DOTA]1-–lisinopril | 4,500 ± 200 | 980 |
| [Cu-DOTA]1-–lisinopril | 4,400 ± 400 | 1,000 |
| lisinopril | 1.9 ± 0.3 | --b |
| Fluorescein-lisinopril | 290 ± 20 | --b |
| DOTA | 7,000 ± 1,000 | --b |
| [Cu-DOTA]2- | 30,000 ± 2,000 | --c |
| EDTA | 7,200 ± 600 | --b |
| [Cu-EDTA]2- | 26,000 ± 5,000 | --c |
| NTA | 32,000 ± 3,000 | --b |
| [Cu-NTA]1- | 36,000 ± 4,000 | --b |
| GGH | > 100,000 | --b |
| [Cu-GGH]1- | 17,000 ± 2,000 | --c |
a
The concentration of M-chelate-lisinopril that inhibited sACE-1 by 20% (TD conc.) was used in time-dependent sACE-1 inactivation experiments so that the remaining 80% activity could be used to monitor the kinetics of inactivation. The concentration required for 20% saturation was higher for cleavage assays, due to the higher concentration of sACE-1 used (20 nM).
b
A time-dependent inactivation experiment was not performed.
c
The concentration used for time-dependent inactivation was the same as that used for the corresponding M-chelate-lisinopril complex.