Table 1. T. cruzi Growth Inhibition, Plasma Protein Binding, Solubility, and Microsomal Stability of Eight Stereoisomers.
|
T. cruzi (IC50, nM) |
|||||||
|---|---|---|---|---|---|---|---|
| cmpd | configuration (C2C5C6) | relative configuration (C5C6) | multimode | amastigote | plasma protein binding (human) | PBS solubility (μM) | microsome stabilitya (mouse) |
| 3 | SRR | trans | 1 | 24 | 99% | 1 | 2% |
| 4 | RRR | trans | 5 | 22 | 99% | 1 | 1% |
| 5 | SSS | trans | 1 | 16 | 99% | 1 | 77% |
| 6 | RSS | trans | 2 | 31 | 99% | 2 | 70% |
| 7 | SRS | cis | 450 | 670 | 95% | 87 | <1% |
| 8 | SSR | cis | 23 | 59 | 95% | 93 | <1% |
| 9 | RRS | cis | 260 | 1200 | 95% | 86 | <1% |
| 10 | RSR | cis | 16 | 75 | ND | 98 | <1% |
a
Amount remaining after 1 h of incubation with 1 μM of the compound.