Table 6.
Calculated ADMET descriptors and toxicity parameters of compounds (3a–3i).
| Compounds | MIC (µg/mL) |
ADMET descriptorsa |
Toxicity parametersb |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Index | Code | H37Rv | MDR-MTB | AS | BBB | CYP2D6 inhibition | Hepatotoxicity | HIA | PPB | AlogP | PSA | AM | SI | OI | AB | DTP | CMR | CFR | CLM | CFM |
| 1 | 3a | 8 | 16 | 1 | 4 | TRUE | TRUE | 1 | TRUE | 5.991 | 61.307 | 1 | 0.152 | 0.971 | 0 | 0 | 0.074 | 0 | 1 | 0.98 |
| 2 | 3b | 32 | 32 | 1 | 1 | TRUE | TRUE | 0 | TRUE | 5.254 | 61.307 | 0 | 0 | 0.627 | 0 | 0 | 0.323 | 0 | 1 | 1 |
| 3 | 3c | 11 | No activity | 1 | 4 | TRUE | TRUE | 1 | TRUE | 5.919 | 61.307 | 0 | 0 | 0.23 | 0 | 0 | 0.449 | 0 | 1 | 1 |
| 4 | 3d | 8 | 32 | 1 | 1 | TRUE | TRUE | 1 | TRUE | 5.74 | 61.307 | 0 | 0 | 0.636 | 0 | 0 | 0.344 | 0 | 1 | 1 |
| 5 | 3e | 32 | 128 | 2 | 1 | TRUE | TRUE | 0 | TRUE | 5.238 | 70.237 | 0 | 0 | 0.019 | 0 | 0 | 0.996 | 0.423 | 1 | 1 |
| 6 | 3f | 128 | No activity | 1 | 4 | TRUE | TRUE | 1 | TRUE | 5.946 | 61.307 | 0 | 0 | 0.271 | 0 | 0 | 0.478 | 0.001 | 1 | 1 |
| 7 | 3g | 32 | No activity | 2 | 1 | TRUE | TRUE | 0 | TRUE | 5.049 | 61.307 | 0 | 0 | 0.359 | 0 | 0 | 0.222 | 0 | 1 | 0.806 |
| 8 | 3h | 64 | No activity | 2 | 1 | FALSE | TRUE | 0 | TRUE | 5.381 | 70.237 | 0 | 0 | 0.605 | 0 | 0 | 0.231 | 0 | 1 | 0.133 |
| 9 | 3i | 11.3 | No activity | 1 | 4 | TRUE | TRUE | 1 | TRUE | 6.243 | 61.307 | 0 | 0 | 1 | 0 | 0 | 0.97 | 0 | 1 | 1 |
|
aKey to the above calculated ADMET descriptors | |||||||
|---|---|---|---|---|---|---|---|
| Aqueous Solubility (AS) |
Blood brain barrier (BBB) penetration |
Human Intestinal Absorption (HIA) |
|||||
| Level | Value | Drug-likeness | Level | Value | Description | Level | Description |
| 0 | log(Sw) < −8.0 | Extremely low | 0 | Very High | Brain-Blood ratio greater than 5:1 | 0 | Good absorption |
| 1 | −8.0 < log(Sw) < −6.0 | No, very low, but possible | 1 | High | Brain-Blood ratio between 1:1 and 5:1 | 1 | Moderate absorption |
| 2 | −6.0 < log(Sw) < −4.1 | Yes, low | 2 | Medium | Brain-Blood ratio between 0.3:1 and 1:1 | 2 | Low absorption |
| 3 | −4.1 < log(Sw) < −2.0 | Yes, good | 3 | Low | Brain-Blood ratio less than 0.3:1 | 3 | Very low absorption |
| 4 | −2.0 < log(Sw) ≤0.0 | Yes, optimal | 4 | Undefined | Outside 99% confidence ellipse | ||
| 5 | 0.0 < log(Sw) | No, too soluble | |||||
|
bKey to the above calculated toxicity parameters | ||
|---|---|---|
| Probability values | Probability level | Description |
| 0.0–0.30 | Low probability | Such a chemical is not likely to produce a positive response in an experimental assay |
| Greater than 0.30 but less than 0.70 | Intermediate probability | |
| Greater than 0.70 | High probability | Likely to produce a positive response in an experimental assay |