Table 6.
Pharmacokinetics properties of potential compounds from Cladosporium spp. and positive control.
| Properties | Compound Name | Coniochaetone | Viriditoxin SC-30532 |
Citrinin HI | (35)-3,8-Dihydroxy-6,7-dimethyl-alpha-tetralone | Azithromycin | ||
|---|---|---|---|---|---|---|---|---|
| A | B | K | ||||||
| Absorption | Water solubility (log mol/L) | − 2.688 | − 2.878 | − 2.772 | − 3.104 | − 4.348 | − 2.33 | − 4.133 |
| Caco-2 permeability (log Papp in 10−6 cm/s) | 0.975 | 0.959 | -0.17 | 0.263 | 0.855 | 1.164 | − 0.211 | |
| Human intestinal absorption (% absorbed) | 95.42 | 94.574 | 60.689 | 93.204 | 83.409 | 94.522 | 45.808 | |
| Skin permeability (log Kp in cm/h) | − 2.857 | − 2.796 | -2.735 | − 2.735 | − 2.896 | − 3.412 | − 2.742 | |
| P-glycoprotein substrate | No | Yes | Yes | Yes | No | No | Yes | |
| P-glycoprotein I inhibitor | No | No | No | Yes | Yes | No | Yes | |
| P-glycoprotein II inhibitor | No | No | No | Yes | No | No | No | |
| Distribution | Human VDss (log L/kg) | 0.059 | 0.25 | − 1.588 | − 1.257 | 0.462 | 0.236 | − 0.214 |
| Human fraction unbound (Fu) | 0.344 | 0.379 | 0.375 | 0.333 | 0.106 | 0.478 | 0.512 | |
| B1313 permeability (log BB) | − 0.004 | 0.126 | − 1.025 | − 2.157 | − 0.677 | − 0.285 | − 1.857 | |
| CNS permeability (log PS) | − 2.04 | − 2.116 | − 3.046 | − 4.009 | − 2.856 | − 2.843 | − 3.777 | |
| Metabolism | CYP2D6 substrate | No | No | No | No | No | No | No |
| CYP3A4 substrate | No | No | No | No | Yes | No | Yes | |
| CYP IA2 inhibitor | Yes | Yes | No | No | No | Yes | No | |
| CYP2C19 inhibitor | No | No | No | No | No | No | No | |
| CYP2C9 inhibitor | No | No | No | No | No | No | No | |
| CYP2D6 inhibitor | No | No | No | No | No | No | No | |
| CYP3A4 inhibitor | No | No | No | No | Yes | No | No | |
| Excretion | Total clearance (log mL/min/kg) | 0.444 | 0.401 | 0.563 | − 0.606 | 0.516 | 0.16 | -0.424 |
| Renal OCT2 substrate | No | No | No | No | No | No | No | |
| Toxicity | AMES toxicity | Yes | No | No | No | No | No | No |
| Human Max. tolerated dose (log mg/kg/day) | 0.081 | 0.274 | 1.109 | 0.378 | 0.548 | 0.537 | 1.027 | |
| hERG I inhibitor | No | No | No | No | No | No | No | |
| hERG II inhibitor | No | No | No | Yes | No | No | No | |
| Oral rat acute toxicity (LD50) (mol/kg) | 2.096 | 2.134 | 2.396 | 2.64 | 2.569 | 2.002 | 2.769 | |
| Oral rat chronic toxicity (LOAEL) (log mg/kg bw/day) | 1.708 | 1.48 | 1.945 | 1.386 | 2.151 | 1.892 | 1.991 | |
| Hepatotoxicity | No | No | No | No | No | No | Yes | |
| Skin sensitization | No | No | No | No | No | No | No | |
| Tetrahymena pyriformis toxicity (log µg/L) | 0.922 | 0.624 | 0.285 | 0.285 | 0.293 | 0.558 | 0.285 | |
| Minnow toxicity (log mM) | 0.908 | 1.728 | 1.714 | − 2.156 | 0.237 | 2.466 | 7.8 | |