Table 4.
QSAR and drug-likeness profile predicted for the Cryptolepis sanguinolenta alkaloids from the SwissADME and ADMETlab web servers.
| Ligand | MW | HBA | HBD | TPSA | cLogPo/w | ESOL logs | ESOL class | GI abs. | LogKp (S.P.) | LP.V | LD.V | SA | D-score |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 11-Isopropylcryptolepine | 276.38 | 0 | 1 | 19.03 | 4.11 | -5.1 | Moderately soluble | High | -4.51 | 0 | 1 | 3.5 | -0.62 |
| Biscryptolepine | 468.59 | 0 | 2 | 38.06 | 5.23 | -7.37 | Poorly soluble | High | -4.42 | 1 | 2 | 5.46 | -0.86 |
| Cryptoheptine | 246.26 | 3 | 1 | 46.01 | 2.95 | -4.06 | Moderately soluble | High | -5.56 | 0 | 1 | 2.43 | -0.49 |
| Cryptolepicarboline | 397.47 | 1 | 0 | 22.75 | 5.57 | -6.99 | Poorly soluble | Low | -4.18 | 1 | 2 | 2.99 | -0.99 |
| Cryptolepine | 232.28 | 1 | 0 | 17.82 | 3.29 | -4.08 | Moderately soluble | High | -5.35 | 0 | 1 | 1.71 | -0.69 |
| Cryptolepinone | 248.28 | 1 | 1 | 37.79 | 2.97 | -4.29 | Moderately soluble | High | -5.28 | 0 | 2 | 2.08 | -0.20 |
| Cryptomisrine | 468.57 | 1 | 3 | 56.92 | 4.94 | -8.00 | Poorly soluble | High | -3.70 | 1 | 2 | 5.01 | -0.48 |
| Cryptoquindoline | 448.52 | 2 | 0 | 35.64 | 5.92 | -7.53 | Poorly soluble | Low | -4.24 | 1 | 2 | 3.2 | -1.18 |
| Cryptospirolepine | 504.58 | 1 | 1 | 45.96 | 5.63 | -7.64 | Poorly soluble | Low | -4.82 | 0 | 2 | 4.95 | -0.34 |
| Hydroxycryptolepine | 250.3 | 1 | 2 | 39.26 | 2.47 | -3.65 | Soluble | High | -5.95 | 0 | 0 | 3.17 | -0.24 |
| Isocryptolepine | 232.28 | 1 | 0 | 17.82 | 3.25 | -4.05 | Moderately soluble | High | -5.38 | 0 | 1 | 1.44 | -0.84 |
| Neocryptolepine | 232.28 | 1 | 0 | 17.82 | 3.47 | -4.32 | Moderately soluble | High | -5.08 | 0 | 2 | 1.56 | -0.38 |
| Quindoline | 217.25 | 2 | 0 | 25.78 | 1.94 | -4.17 | Moderately soluble | High | -5.10 | 0 | 2 | 1.57 | -1.03 |
MW: molecular weight; HBA: hydrogen bond acceptor; HBD: hydrogen bond donor; TPSA: topological polar surface area; cLogPo/w: lipophilicity; ESOL logs: water solubility; ESOL class: classification of water solubility; GI abs.: gastrointestinal absorption; LogKp (S.P.): skin permeability; LP.V: number of Lipinski's rules violated; LD.V: lead-likeness violation; SA: synthetic ability; D-score: drug-likeness model score. All alkaloids violated none or only one of Lipinski's rules. Cryptomisirine donates the most hydrogen bonds followed by biscryptolepine and hydroxycryptolepine. Cryptoheptine had the ability to accept the most hydrogen bonds followed by cryptoquindoline and quindoline. With a similar molecular landscape, all 13 alkaloids were largely hydrophobic, with most being moderately soluble to poorly soluble. Only hydroxycryptolepine was completely soluble. All ligands have the ability to cross the blood-brain barrier with most having high gastrointestinal absorption indices.