Table 4 The ADMET parameters of polyphenols from M. fruticosa spp. brachycalyx via pkcsm software
Hexose polymer | 5-O-Caffeoylquinic acid | Caffeic acid | Kaempferol-3-O-glucuronide | Rutin | Malonyl-caffeoyl-quinic acid | 6,8-Dimethoxy-7-hydroxycoumarin | Shikimoyl-hexose | |
|---|---|---|---|---|---|---|---|---|
Absorption | ||||||||
Water solubility (log mol/L) | − 1.381 | − 2.449 | − 2.33 | − 2.866 | − 2.892 | − 2.965 | − 2.458 | − 0.214 |
Caco2 permeability (log Pc cm/s) | − 0.359 | − 0.84 | 0.634 | − 0.884 | − 0.949 | − 0.744 | 0.378 | − 0.481 |
Intestinal absorption (% A) | 30.68 | 36.38 | 69.41 | 25.17 | 23.45 | 8.338 | 95.59 | 6.657 |
Skin permeability (log Kp) | − 2.913 | − 2.735 | − 2.722 | − 2.735 | − 2.735 | − 2.735 | − 2.945 | − 2.747 |
P-glycoprotein substrate | No | Yes | No | Yes | Yes | Yes | No | Yes |
P-glycoprotein I inhibitor | No | No | No | No | No | No | No | No |
P-glycoprotein II inhibitor | No | No | No | No | No | No | No | No |
Distribution | ||||||||
VDssa | − 0.069 | 0.581 | − 1.098 | 1.295 | 1.663 | 0.147 | − 0.354 | 0.283 |
Fraction unbound | 0.891 | 0.658 | 0.529 | 0.28 | 0.187 | 0.43 | 0.316 | 0.663 |
BBB permeabilityb (log BB) | − 0.895 | − 1.407 | − 0.647 | − 1.441 | − 1.899 | − 2.069 | − 0.377 | − 1.051 |
CNS permeabilityc (log PS) | − 3.359 | − 3.856 | − 2.608 | − 3.955 | − 5.178 | − 3.71 | − 2.473 | − 5.681 |
Metabolism | ||||||||
CYP2D6 substrate | No | No | No | No | No | No | No | No |
CYP3A4 substrate | No | No | No | No | No | No | No | No |
CYP1A2 inhibitor | No | No | No | No | No | No | Yes | No |
CYP2C19 inhibitor | No | No | No | No | No | No | No | No |
CYP2C9 inhibitor | No | No | No | No | No | No | No | No |
CYP2D6 inhibitor | No | No | No | No | No | No | No | No |
CYP3A4 inhibitor | No | No | No | No | No | No | No | No |
Excretion | ||||||||
Total clearance (log ml/min/kg) | 0.907 | 0.307 | 0.508 | 0.503 | − 0.369 | − 0.036 | 0.713 | 1.524 |
Renal OCT2 substrate | No | No | No | No | No | No | No | No |
Toxicity | ||||||||
AMES toxicity | No | No | No | No | No | No | No | No |
Max. tolerated dose (log mg/kg/day) | 1.865 | − 0.134 | 1.145 | 0.46 | 0.452 | 1.029 | 0.56 | 1.208 |
hERG I inhibitor | No | No | No | No | No | No | No | No |
hERG II inhibitor | No | No | No | No | Yes | No | No | No |
Oral rat acuted Toxicity | 0.955 | 1.973 | 2.383 | 2.513 | 2.491 | 2.389 | 2.326 | 1.958 |
Oral rat chronice Toxicity | 3.553 | 2.982 | 2.092 | 4.641 | 3.673 | 3.756 | 1.825 | 4.068 |
Hepatotoxicity | No | No | No | No | No | No | No | No |
Skin sensitization | No | No | No | No | No | No | No | No |
T. Pyriformis toxicity (log µg/L) | 0.285 | 0.285 | 0.293 | 0.285 | 0.285 | 0.285 | 0.431 | 0.285 |
Minnow toxicity (log mM) | 5.494 | 5.741 | 2.246 | 6.898 | 7.677 | 5.661 | 1.862 | 5.541 |