Table 2.
ADME properties of top selected compounds.
| Property | Parameters | Dithymoquinone (DTQ) | Calycosin | Limonin | Nigellidine |
|---|---|---|---|---|---|
| Absorption | Water solubility (log mol/L) | −3.654 | −3.423 | −4.041 | −3.651 |
| Caco2 permeability (log Papp in 10–6 cm/s) | 1.367 | 0.96 | 0.922 | 1.304 | |
| Intestinal absorption (human) (% Absorbed) | 100 | 95.098 | 100 | 95.368 | |
| Skin permeability (log Kp) | −3.189 | −2.747 | −2.832 | −2.916 | |
| P-glycoprotein substrate (Yes/No) | No | Yes | No | No | |
| P-glycoprotein I inhibitor (Yes/No) | Yes | No | Yes | Yes | |
| P-glycoprotein II inhibitor (Yes/No) | No | No | No | No | |
| Distribution | VDss (human) (log L/kg) | −0.026 | −0.326 | 0.265 | 0.508 |
| Fraction unbound (human) (Fu) | 0.188 | 0.057 | 0.145 | 0.123 | |
| BBB permeability (log BB) | −0.118 | −0.315 | −0.844 | −0.104 | |
| CNS permeability (log PS) | −2.719 | −2.24 | −3.07 | −2.16 | |
| Metabolism | CYP2D6 substrate (Yes/No) | No | No | No | No |
| CYP3A4 substrate (Yes/No) | Yes | Yes | Yes | Yes | |
| CYP1A2 inhibitor (Yes/No) | No | Yes | No | No | |
| CYP2C19 inhibitor (Yes/No) | No | Yes | No | Yes | |
| CYP2C9 inhibitor (Yes/No) | No | Yes | No | No | |
| CYP2D6 inhibitor (Yes/No) | No | No | No | No | |
| CYP3A4 inhibitor (Yes/No) | No | Yes | No | No | |
| Excretion | Total clearance (log ml/min/kg) | −0.016 | 0.18 | 0.088 | 0.511 |
| Renal OCT2 substrate (Yes/No) | Yes | No | No | Yes | |
| Toxicity | AMES toxicity (Yes/No) | Yes | Yes | No | No |
| Max. tolerated dose (human) (log mg/kg/day) | 0.534 | 0.141 | −0.508 | −0.425 | |
| hERG I inhibitor (Yes/No) | No | No | No | No | |
| hERG II inhibitor (Yes/No) | No | No | No | No | |
| Oral Rat Acute Toxicity (LD50) (mol/kg) | 1.649 | 2.127 | 3.452 | 2.423 | |
| Oral Rat Chronic Toxicity (LOAEL) (log mg/kg_bw/day) | 1.53 | 1.796 | 1.911 | 1.081 | |
| Hepatotoxicity (Yes/No) | No | No | No | Yes | |
| Skin sensitization (Yes/No) | No | No | No | No | |
| T. pyriformis toxicity (log ug/L) | 0.445 | 0.521 | 0.286 | 1.437 | |
| Minnow toxicity (log mM) | 1.323 | 0.397 | 0.446 | 1.17 |