Table 3.
Physicochemical properties, lipophilicity, water solubility, pharmacokinetics, druglikeness and medicinal chemistry friendliness of the eight potential trifunctional peptides as analyzed by using SwissADME
| Parameters | Peptides | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| PKRF | PHYNN | PNWKIN | AIRAMPL | PHWNIN | TKHGGRINTL | ERHHRGGRGRQS | VEDKGMMHQQRMMEKAMNIPRMCGTMQRKCRMS | ||
| Physicochemical properties | Number of heavy atoms | 39 | 46 | 55 | 53 | 56 | 77 | 101 | 267 |
| Number of aromatic heavy atoms | 6 | 11 | 9 | 0 | 14 | 5 | 10 | 5 | |
| Fraction Csp3 | 0.58 | 0.43 | 0.56 | 0.76 | 0.47 | 0.67 | 0.56 | 0.70 | |
| Number of rotatable bonds | 21 | 21 | 28 | 30 | 26 | 47 | 65 | 180 | |
| Number of H-bond acceptors | 8 | 11 | 11 | 10 | 11 | 18 | 24 | 55 | |
| Number of H-bond donors | 9 | 10 | 11 | 10 | 11 | 19 | 30 | 58 | |
| Molar refractivity | 149.93 | 160.79 | 202.96 | 206.63 | 202.46 | 273.98 | 350.66 | 1001.83 | |
| TPSA (Å2) | 224.55 | 300.82 | 322.82 | 316.33 | 325.48 | 525.37 | 789.00 | 1944.79 | |
| Lipophilicity | Consensus log Po/w | − 0.80 | − 3.14 | − 1.60 | − 0.36 | − 1.50 | − 4.62 | − 8.94 | − 12.55 |
| Water solubility | Log S (ESOL) | 0.33 | 0.79 | − 0.45 | − 0.59 | − 0.71 | 1.14 | 3.98 | 2.50 |
| Class (ESOL) | Highly soluble | Highly soluble | Very soluble | Very soluble | Very soluble | Highly soluble | Highly soluble | Highly soluble | |
| Pharmacokinetics | GI absorption | Low | Low | Low | Low | Low | Low | Low | Low |
| P-gp substrate | No | No | Yes | Yes | Yes | Yes | Yes | Yes | |
| CYP1A2 inhibitor | No | No | No | No | No | No | No | 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 | |
| Druglikeness | Lipinski’s rule (number of violations) | No (3) | No (3) | No (3) | No (3) | No (3) | No (3) | No (3) | No (3) |
| Bioavailability score | 0.17 | 0.17 | 0.17 | 0.17 | 0.17 | 0.17 | 0.17 | 0.17 | |
| Medicinal chemistry | Leadlikeness (number of violations) | No (2) | No (2) | No (2) | No (2) | No (2) | No (2) | No (2) | No (2) |
| Synthetic accessibility | 4.87 | 5.37 | 6.52 | 7.16 | 6.49 | 9.34 | 10.00 | 10.00 | |
Fraction Csp3 ratio of sp3 hybridized carbons over the total carbon count of the molecule, H-bond hydrogen bond, TPSA topological polar surface area, log Po/w partition coefficient between n-octanol and water, ESOL estimated solubility, GI gastrointestinal, P-gp permeability glycroprotein, CYP1A2 cytochrome P450 1A2, CYP2C19 cytochrome P450 2C19, CYP2C9 cytochrome P450 2C9, CYP2D6 cytochrome P450 2D6, CYP3A4 cytochrome P450 3A4