Table 4 Computational parameters for ADME profile and toxicity risks of compounds isolated from Malagasy medicinal plants traditionally used to treat cancer
Property | Parameters | Compounds | |||
|---|---|---|---|---|---|
1 | 2 | 3 | 4 | ||
Absorption | Water solubility(log mol/L) | − 3.803 | − 3.671 | − 6.596 | − 6.131 |
Caco2 permeability(log Papp in 10–6 cm/s) | 1.038 | 1.283 | 1.111 | 0.761 | |
Intestinal absorption (human) (% Absorbed) | 89.82 | 73.349 | 98.351 | 98.371 | |
Skin Permeability (log Kp) | − 2.968 | − 3.179 | − 2.202 | − 3.04 | |
P-glycoprotein substrate(Yes/No) | Yes | Yes | No | No | |
P-glycoprotein I inhibitor(Yes/No) | Yes | Yes | Yes | Yes | |
P-glycoprotein II inhibitor | No | No | No | Yes | |
Distribution | VDss (human)(log L/kg) | 0.032 | 0.349 | 1.105 | -0.122 |
Fraction unbound (human) | 0.137 | 0.128 | 0 | 0 | |
BBB permeability (log BB) | − 0.211 | − 0.427 | 0.749 | − 0.104 | |
CNS permeability (log PS) | − 2.858 | − 3.279 | − 1.341 | − 1.249 | |
Metabolism | CYP2D6 substrate | No | No | No | No |
CYP3A4 substrate | No | No | Yes | Yes | |
CYP1A2 inhibitor | No | No | Yes | No | |
CYP2C19 inhibitor | No | No | Yes | No | |
CYP2C9 inhibitor | No | No | Yes | No | |
CYP2D6 inhibitor | No | No | No | No | |
CYP3A4 inhibitor | Yes | No | No | No | |
Excretion | Total clearance | 0.398 | 0.074 | 0.226 | − 0.026 |
Renal OCT2 substrate | No | No | Yes | No | |
Toxicity | AMES toxicity | Yes | No | No | No |
Max. tolerated dose (human)(log mg/kg/day) | − 0.103 | − 0.461 | 0.701 | − 0.026 | |
hERG I inhibitor | No | No | No | No | |
hERG II inhibitor | No | No | No | No | |
Oral Rat Acute Toxicity (LD50)(mol/kg) | 2.228 | 2.388 | 2.178 | 3.054 | |
Oral Rat Chronic Toxicity (LOAEL)(log mg/kg_bw/day) | 1.735 | 2.133 | 1.009 | 2.1 | |
Hepatotoxicity | Yes | No | No | No | |
Skin Sensitization | No | No | No | No | |
T. Pyriformis toxicity(log ug/L) | 0.389 | 0.313 | 1.689 | 0.333 | |
Minnow toxicity (log mM) | 1.897 | 0.57 | − 1.007 | − 1.493 | |