Table 2.
ADME/Tox predicted values of the disulfide alkaloids.
| Cpd ID | Drug-likeness (no. of violations) | Oral bioavailability prediction | Cardiotoxicity prediction | Blood-brain barrier (BBB) penetration | Skin permeability | Protein binding | Primary metabolism | Passive membrane permeability | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ro5 | Ro3 | QPlogS | %PHOA | QPPCaco (nm/sec) | QPlogHERG | QPlogBB | CNS | QPPMDCK (nm/sec) | QPlogKp | QPlogKhsa | #metab | Membrane dG insert (kcal/Mol) | Log perm RRCK (cm/s) | |
| A1 | 0 | 0 | -1.78 | 100 | 3034.94 | -3.60 | 0.21 | 1 | 4518.15 | -1.84 | -0.51 | 1 | 6.229630 | -4.359774 |
| A2 | 0 | 0 | -2.58 | 100 | 3038.80 | -4.23 | 0.15 | 1 | 7490.62 | -1.64 | -0.36 | 1 | 5.336709 | -4.376275 |
| A3 | 0 | 0 | -2.83 | 100 | 1523.45 | -4.60 | -0.16 | 0 | 1873.12 | -1.80 | -0.17 | 3 | 10.959890 | -4.673919 |
| A4 | 0 | 0 | -2.09 | 100 | 8470.62 | -3.85 | 0.59 | 2 | 10000 | -0.83 | -0.27 | 1 | 2.591768 | -4.204556 |
| A5 | 0 | 0 | -1.61 | 100 | 5091.54 | -3.68 | 0.41 | 1 | 8584.47 | -1.37 | -0.57 | 2 | 6.893223 | -4.376285 |
| A6 | 0 | 0 | -3.61 | 100 | 8544.57 | -4.62 | 0.59 | 2 | 10000 | -0.56 | 0.14 | 0 | 4.415087 | -4.375935 |
| A7 | 0 | 0 | -2.73 | 100 | 9906.04 | -3.89 | -0.09 | 0 | 10000 | -0.64 | -0.11 | 0 | -0.264257 | -4.094258 |
| A8 | 0 | 0 | -2.90 | 100 | 9906.04 | -3.55 | 0.15 | 1 | 10000 | -0.83 | -0.06 | 1 | 1.752616 | -4.147198 |
| B9 | 0 | 0 | -2.71 | 85 | 303.06 | -5.98 | -0.05 | 1 | 626.22 | -4.03 | -0.12 | 1 | 4.308330 | -4.446987 |
| B10 | 0 | 0 | -2.86 | 100 | 1714.01 | -3.86 | 0.05 | 1 | 5095.63 | -2.31 | -0.29 | 1 | 11.416972 | -4.640013 |
| B11 | 0 | 0 | -3.53 | 100 | 6345.49 | -4.15 | 0.67 | 2 | 10000 | -1.15 | -0.04 | 1 | 2.017210 | -4.245295 |
| B12 | 0 | 0 | -2.09 | 90 | 953.75 | -3.17 | -0.33 | 0 | 1135.252 | -3.188 | -0.45 | 0 | 6.398424 | -4.404494 |
QPlogS: predicted aqueous solubility (-6.5-0.5); %PHOA: predicted human oral absorption on 0 to 100% scale (>80%: great, <25% is poor); QPPCaco: predicted apparent Caco-2 cell (a model for the gut-blood barrier) permeability in nm/sec (<25: poor, >500: great); QPlogHERG: predicted IC50 value for blockage of HERG K+ channels (concern below -5); QPlogBB: predicted brain/blood partition coefficient (-3 to 12.0); CNS: predicted central nervous system activity on a –2 (inactive) to +2 (active) scale; QPPMDCK: predicted apparent MDCK cell permeability in nm/sec. MDCK cells are considered to be a good mimic for the blood-brain barrier (<25: poor, >500: great). QikProp predictions of Caco and MDCK are for nonactive transport; QPlogKp: predicted skin permeability, log Kp. (-8.0-1.0). QPlogKhsa: prediction of binding to human serum albumin (-1.5 to 1.5); #metab: number of likely metabolic reactions (1-8).