Table 8.
In silico prediction of physicochemical and pharmacokinetics properties of top binding alkaloids.
| (a) Lipinski filter analysis | |||||
|---|---|---|---|---|---|
| Lipinski filters |
Cryptospirolepine |
10-Hydroxyusambarensine |
Cryptoquindoline |
Isocryptolepine |
Strychnopentamine |
| Molecular weight (g/mol) | 504.58 | 448.56 | 448.52 | 232.28 | 459.75 |
| Num. heavy atoms | 39 | 34 | 35 | 18 | 41 |
| Num. rotatable bonds | 2 | 2 | 1 | 0 | 4 |
| Num. H-bond acceptors | 1 | 3 | 2 | 1 | 4 |
| Hydrogen bond donor | 1 | 3 | 0 | 0 | 3 |
| cLogP | 3.75 | 3.31 | 4.02 | 4.02 | 3.51 |
| Molar refractivity | 161.96 | 142.46 | 145.65 | 76.01 | 180.14 |
| Lipinski violation |
1 |
0 |
0 |
0 |
1 |
| (b) Admet SAR | |||||
| Absorption (Probability) | |||||
| Blood-Brain Barrier | BBB+ (0.99) | BBB+ (0.83) | BBB+ (0.95) | BBB+ (0.97) | BBB+ (0.71) |
| Human intestinal absorption | HIA+ (0.97) | HIA+ (0.98) | HIA+ (0.99) | HIA+ (0.99) | HIA+ (0.98) |
| Bioavailability score | 0.55 | 0.55 | 0.55 | 0.55 | 0.55 |
| Caco-2 permeability | Caco2+ (0.74) | Caco2+ (0.53) | Caco2+ (0.76) | Caco2+ (0.67) | Caco2+ (0.53) |
| P-glycoprotein substrate | Nonsubstrate (0.50) | Substrate (0.91) | Noninhibitor (0.69) | Noninhibitor (0.74) | Noninhibitor (0.87) |
| P-glycoprotein inhibitor | Noninhibitor (0.84) | Noninhibitor (0.60) | Noninhibitor (0.72) | Noninhibitor (0.74) | Noninhibitor (0.54) |
| Renal organic cation transporter | Noninhibitor (0.70) | Inhibitor (0.80) | Noninhibitor (0.67) | Noninhibitor (0.54) | Noninhibitor (0.70) |
| Distribution (Probability) | |||||
| Subcellular localization | Mitochondria (0.70) | Mitochondria (0.65) | Mitochondria (0.55) | Mitochondria (0.76) | Mitochondria (0.57) |
| Metabolism | |||||
| CYP450 Substrate | Substrate (0.69) | Substrate (0.53) | Substrate (0.86) | Substrate (0.65) | Nonsubstrate (0.79) |
| Noninhibitor (0.76) | Noninhibitor (0.83) | Noninhibitor (0.86) | Noninhibitor (0.81) | Inhibitor (0.54) | |
| Toxicity | |||||
| AMES toxicity | Non AMES toxic (0.61) | Non AMES toxic (0.75) | AMES toxic (0.89) | AMES toxic (0.80) | Non AMES toxic (0.68) |
| Carcinogens | Noncarcinogens (0.94) | Noncarcinogens (0.97) | Noncarcinogens (0.92) | Noncarcinogens (0.96) | Noncarcinogens (0.95) |
| Acute oral toxicity | III (0.50) | III (0.51) | III (0.67) | III (0.72) | III (0.56) |
| Rat acute toxicity LD50 (mol/kg) | 2.4992 | 2.7896 | 2.4420 | 2.3770 | 2.7631 |
| Aqueous solubility (LogS) | –3.5692 | –2.7626 | –3.1120 | –3.21 | –2.6192 |
| Pharmacokinetics | |||||
| GI absorption | Low | High | Low | High | High |
| Log Kp (skin permeation) (cm/s) | –4.82 | –5.70 | –3.97 | –5.38 | –5.82 |