Table 4:
Cytotoxicity and inhibition of human proteasomes (hCP) measured in Jurkat lysate for Px/Py analogs. Assays were performed in biological triplicate (n=3) and confirmed in technical triplicate. The IC50 values were calculated using a nonlinear dose response model in GraphPad Prism 6.0 and are reported with the corresponding SD. ND: Not determined.
 |
| IC50 (μΜ) ± SD |
|||||||
|---|---|---|---|---|---|---|---|
| Substitution | hCP Inhibition | Cytotoxicity | |||||
| Compound | Px | Py | hβ5 | hβ2 | MCF7 | MDA-MB-231 | RPMI 8226 |
| 2 | i-Pr | i-Pr | 0.0070 ± 0.0003 | 1.430 ± 0.089 | 1.853 ± 0.261 | 0.287 ± 0.008 | 0.191 ± 0.015 |
| 5a | H | i-Pr | 0.0027 ± 0.0001 | 0.261 ± 0.008 | 2.085 ± 0.872 | 0.678 ± 0.045 | 0.762 ± 0.106 |
| 5b | Bn | i-Pr | 0.0078 ± 0.0004 | 3.716 ± 0.294 | 6.945 ± 1.031 | 3.756 ± 0.435 | 2.608 ± 0.206 |
| 5c | i-Pr | Bn | 0.0057 ± 0.0005 | 1.777 ± 0.222 | 2.748 ± 0.229 | 3.349 ± 0.263 | 1.103 ± 0.067 |
| 5d | Bn | Bn | 0.0116 ± 0.0007 | 2.713 ± 0.130 | 6.249 ± 0.636 | 5.211 ± 0.187 | 1.176 ± 0.091 |
| 5e | t-Bu | i-Pr | 0.0228 ± 0.0009 | 5.053 ± 0.688 | 2.288 ± 0.141 | 0.699 ± 0.021 | 0.748 ± 0.035 |
| 5f | i-Pr | t-Bu | 0.0098 ± 0.0005 | 3.749 ± 0.263 | 1.137 ± 0.078 | 1.910 ± 0.119 | 1.748 ± 0.094 |
| 5g | t-Bu | t-Bu | 0.0359 ± 0.0053 | 3.517 ± 0.109 | 1.905 ± 0.130 | 0.673 ± 0.031 | 1.217 ± 0.059 |
| 5h | i-Bu | i-Pr | 0.0050 ± 0.0004 | 2.953 ± 0.135 | 2.465 ± 0.328 | 1.453 ± 0.183 | 2.243 ± 0.188 |
| 5i | i-Pr | i-Bu | 0.0077 ± 0.0004 | 1.509 ± 0.160 | 0.332 ± 0.012 | 0.219 ± 0.008 | 0.286 ± 0.011 |
| 5j | CH2O-Bn | i-Pr | 0.0077 ± 0.0008 | 0.759 ± 0.020 | 3.452 ± 0.236 | 2.859 ± 0.056 | 1.706 ± 0.131 |
| 5k | i-Pr | CH2O-Bn | 0.0031 ± 0.0002 | 1.558 ± 0.062 | 0.416 ± 0.025 | 0.074 ± 0.006 | 0.041 ± 0.002 |
|
Carfilzomib (Cfz) |
0.0096 ± 0.0006 | 0.203 ± 0.005 | 0.0041 ± 0.0001 | 0.0044 ± 0.0001 | 0.0067 ± 0.0002 | ||
| Cystargolide B | 0.90 ± 0.11 | ND | 84.7 ± 18.6 | ND | ND | ||