CXCR4-dependent effects and cellular toxicity of trans-IV metal complexes.
| CXCR4-mediated effects, IC50 (nM) | CC50 (μM) | |||
|---|---|---|---|---|
| Anti-HIV activitya | CXCL12 bindingbx | Ca2+ signallingc | Cellular toxicityd | |
| 1 | >5000 | >1000 | >10 000 | >100 |
| [Ni1]2+ | >5000 | >3000 | >2000 | 26.0 ± 6.4 |
| [Cu1]2+ | >5000 | >10 000 | >2000 | 68.2 ± 3.4 |
| [Zn1]2+ | >5000 | >1000 | >2000 | >100 |
| 2 | >5000 | >1000 | >10 000 | >100 |
| [Ni22]4+ | >5000 | >1000 | >2000 | 11.7 ± 2.8 |
| [Cu22]4+ | >5000 | >1000 | >2000 | 37.9 ± 7.1 |
| [Zn22]4+ | 642.0 ± 193.7 | 5.5 ± 0.7 | 67.5 ± 38.9 | 46.7 ± 4.0 |
| 3 | >5000 | >1000 | >10 000 | >50 |
| [Ni23]4+ | >5000 | 668.0 ± 106.1 | >2000 | 10.6 ± 0.7 |
| [Cu23]4+ | 332.5 ± 6.4 | 25.5 ± 3.5 | 108.0 ± 11.3 | 32.7 ± 0.3 |
| [Zn23]4+ | 327.0 ± 25.5 | 4.5 ± 0.7 | 72.5 ± 38.9 | 40.7 ± 0.2 |
| AMD3100 | 20.0 ± 1.4 | 18.0 ± 4.2 | 203.5 ± 19.429 | >100 |
| [Ni2AMD3100]4+ | 7.942,e | ND | 2.042,e | >10042,e |
| [Cu2AMD3100]4+ | 22.442,e | ND | 48.742,e | >10042,e |
| [Zn2AMD3100]4+ | 6.842,e | ND | 2.942,e | >10042,e |
a
Concentration required to inhibit the replication of HIV-1 strain NL4-3 (×4) by 50% in MT-4 cells.
b
Concentration required to inhibit CXCL12 binding by 50%.
c
Concentration required to reduce the level of Ca2+ ions observed during a normal signalling process by 50% in U87.CD4.CXCR4 cells.
d
Concentration required to reduce cell viability by 50% in MT-4 cells.
e
Concentration values published in μg mL−1 converted to nM.