Table 3.
Physicochemical properties and ADMET predictions of the lamellarin analogues and virtual hit candidates.
| Compound | Raltgravir | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 22850303 | 27553460 | 24578440 | 27591056 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Drug-like score | 4.13 | 3.76 | 4.80 | 4.36 | 4.81 | 3.82 | 2.90 | 4.36 | 4.80 | 5.35 | 5.01 | 5.10 | 4.80 |
| BBB | 0.043 | 0.288 | 0.035 | 0.026 | 0.168 | 0.050 | 0.052 | 0.073 | 0.029 | 0.027 | 0.800 | 0.045 | 0.038 |
| Buffer solubility (mg/L) | 16098.50 | 47.658 | 1.0799 | 0.9748 | 2.787 | 1.281 | 1.492 | 8.557 | 1.016 | 4.841 | 0.472 | 5.153 | 1.456 |
| Caco-2 | 20.04 | 16.556 | 25.123 | 27.999 | 18.939 | 2.269 | 1.887 | 28.36 | 25.48 | 29.10 | 50.66 | 27.45 | 25.68 |
| CYP2C19 inhibition | - | + | + | + | + | - | - | + | - | - | - | - | - |
| CYP2C9 inhibition | - | + | + | + | + | + | + | + | + | + | + | - | + |
| CYP2D6 inhibition | - | - | - | - | - | - | - | - | - | - | - | - | - |
| CYP2D6 substrate | - | - | - | - | - | - | - | - | - | - | - | - | - |
| CYP3A4 inhibition | + | + | + | + | + | + | + | + | + | - | - | + | - |
| CYP3A4 substrate | - | + | + | + | + | + | + | + | + | + | + | + | + |
| HIA (%) | 76.78 | 83.05 | 95.93 | 95.81 | 94.41 | 99.05 | 95.23 | 95.61 | 95.29 | 96.04 | 97.41 | 96.27 | 96.08 |
| Pgp inhibition | - | + | + | + | + | + | + | + | + | - | + | + | - |
| PPB (%) | 48.76 | 100.00 | 89.37 | 89.61 | 87.80 | 98.67 | 100.00 | 88.75 | 88.74 | 96.33 | 96.13 | 89.71 | 97.46 |
| PWS (mg/L) | 909.002 | 0.122 | 0.006 | 0.006 | 0.012 | 0.002 | 0.001 | 0.072 | 0.651 | 2.799 | 0.002 | 17.902 | 0.102 |
| carcino_Mouse | - | - | - | - | - | - | - | - | - | - | - | + | + |
| carcino_Rat | - | - | + | + | + | - | + | + | + | - | - | - | - |
| hERG_inhibition | Medium | Medium | Medium | Medium | Medium | Medium | Low | Medium | Medium | High | Medium | Medium | Ambiguous |
| TA100_10RLI | - | - | - | - | - | - | - | - | - | - | - | + | - |
| TA100_NA | + | - | - | - | - | - | - | - | - | - | - | - | - |
| TA1535_10RLI | - | - | - | - | - | - | - | - | - | - | - | + | - |
| TA1535_NA | - | - | - | - | - | + | - | - | - | - | - | - | - |
BBB = blood brain barrier penetration, Caco-2 = permeation of Caco-2 colorectal adenocarcinoma cells, CYP2C19 = cytochrome P4502C19, CYP2C9 = cytochrome P4502C9, CYP3A4 = cytochrome P4503A4, CYP2D6 = cytochrome P4502D6, Pgp = P-glycoprotein, HIA = human intestinal absorption, PPB = plasma binding protein, PWS = pure water solubility, TA100_10RLI/1535_10_RLI = TA100/TA1535 strain with metabolic activation by rat liver homogenate, TA100_NA/1535_NA = TA100/1535 strain with no metabolic activation.