Table 3 The ADMET parameters of polyphenols from R. coriaria via pkcsm software
Galloyl hexoside | Malvidin-3,5-diglucoside | Galloyl dihexoside | Syringic acid | Galloyl-di-O-hexoside | Gallic acid | Tricetin | Syringic acid-O-hexoside | Quinic acid | |
|---|---|---|---|---|---|---|---|---|---|
Absorption | |||||||||
Water solubility (log mol/L) | − 1.89 | − 2.866 | − 2.705 | − 2.223 | − 2.895 | − 2.56 | − 3.028 | − 2.501 | − 0.911 |
Caco2 permeability (log Pc cm/s) | − 0.795 | − 1.345 | − 0.866 | 0.495 | − 1.682 | − 0.081 | − 0.272 | − 0.485 | − 0.418 |
Intestinal absorption (% A) | 37.36 | 0 | 0 | 73.08 | 15.64 | 43.37 | 78.37 | 25.25 | 21.667 |
Skin Permeability (log Kp) | − 2.735 | − 2.735 | − 2.735 | − 2.735 | − 2.735 | − 2.735 | − 2.735 | − 2.735 | − 2.735 |
P-glycoprotein substrate | No | Yes | Yes | Yes | Yes | No | Yes | Yes | No |
P-glycoprotein I inhibitor | No | No | No | No | No | No | No | No | No |
P-glycoprotein II inhibitor | No | No | No | No | No | No | No | No | No |
Distribution | |||||||||
VDssa | 0.517 | 1.205 | − 0.058 | − 1.443 | 1.614 | − 1.855 | 0.932 | − 0.782 | − 0.817 |
Fraction unbound | 0.818 | 0.247 | 0.428 | 0.601 | 0.347 | 0.617 | 0.208 | 0.645 | 0.737 |
BBB permeabilityb (log BB) | − 1.616 | − 2.459 | − 1.665 | − 0.191 | − 2.435 | − 1.102 | − 1.38 | − 1.434 | − 1.085 |
CNS permeabilityc (log PS) | − 4.465 | − 5.358 | − 7.028 | − 2.701 | − 4.668 | − 3.74 | − 3.557 | − 4.147 | − 4.399 |
Metabolism | |||||||||
CYP2D6 substrate | No | No | No | No | No | No | No | No | Yes |
CYP3A4 substrate | No | No | No | No | No | No | No | No | No |
CYP1A2 inhibitor | No | No | No | No | No | No | Yes | No | No |
CYP2C19 inhibitor | No | No | No | No | No | No | No | No | No |
CYP2C9 inhibitor | No | No | No | No | No | No | No | No | No |
CYP2D6 inhibitor | No | No | No | No | No | No | No | No | No |
CYP3A4 inhibitor | No | No | No | No | No | No | No | No | No |
Excretion | |||||||||
Total clearance (log ml/min/kg) | 0.512 | − 0.077 | 0.535 | 0.646 | 0.47 | 0.518 | 0.513 | 0.646 | 0.639 |
Renal OCT2 substrate | No | No | No | No | No | No | No | No | No |
Toxicity | |||||||||
AMES toxicity | No | No | No | No | No | No | No | No | No |
Maximum tolerated dosed | 0.22 | 0.468 | 0.2 | 1.374 | 0.453 | 0.7 | 0.545 | 1.168 | 2.148 |
hERG I inhibitor | No | No | No | No | No | No | No | No | No |
hERG II inhibitor | No | Yes | Yes | No | Yes | No | No | No | No |
Oral rat acutee Toxicity | 2.414 | 2.5 | 2.493 | 2.157 | 2.505 | 2.218 | 2.421 | 2.389 | 1.539 |
Oral rat chronicf Toxicity | 4.092 | 4.843 | 5.701 | 2.415 | 4.675 | 3.06 | 2.551 | 3.718 | 3.433 |
Hepatotoxicity | No | No | No | No | No | No | No | Yes | No |
Skin Sensitization | No | No | No | No | No | No | No | No | No |
T. Pyriformis toxicity (log µg/L) | 0.285 | 0.285 | 0.285 | 0.281 | 0.285 | 0.285 | 0.31 | 0.285 | 0.285 |
Minnow toxicity (log mM) | 6.856 | 8.253 | 6.19 | 2.554 | 8.255 | 3.188 | 4.09 | 6.404 | 3.812 |