Table 2 Physicochemical and pharmacokinetic properties of ART-THY hybrids, parental and control compounds
Compound | MW (g/mol) | N.RB | N.HBAs | N.HBDs | Physicochemical properties | Pharmacokinetics | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
TPSA at pH 7.4 (Å2) | Lipophilicity | Water solubility at pH 7.4 | Absorption | Distribution | ||||||||
log P | log S | mol/L | HIA (%) | PCaco-2 (nm/s) | PPB (%) | BBB (Cbrain/Cblood) | ||||||
Parental ligands | ||||||||||||
ART | 282.33 | 0 | 5 | 0 | 53.99 | 1.68 | − 2.69 | 0.0020 | 96.31 | 30.32 | 93.36 | 1.30 |
ARA | 384.42 | 5 | 8 | 1 | 103.35 | 1.70 | − 1.62 | 0.0238 | 83.94 | 13.21 | 90.61 | 0.01 |
THY | 164.20 | 1 | 2 | 0 | 34.14 | 2.51 | − 2.66 | 0.0021 | 99.28 | 23.03 | 100.00 | 1.78 |
Artemisinin–thymoquinone hybrids | ||||||||||||
T1 | 588.69 | 11 | 10 | 0 | 123.66 | 4.69 | − 6.69 | 0.0076 | 97.00 | 21.18 | 93.30 | 0.02 |
T2 | 602.71 | 12 | 10 | 0 | 123.66 | 5.15 | − 7.00 | 0.0037 | 97.52 | 24.18 | 94.30 | 0.03 |
T3 | 574.66 | 10 | 10 | 0 | 123.66 | 4.24 | − 6.38 | 0.0002 | 96.42 | 22.11 | 92.79 | 0.02 |
T4 | 530.65 | 8 | 8 | 0 | 97.36 | 4.79 | − 6.83 | 0.0001 | 99.10 | 36.05 | 93.54 | 0.07 |
T5 | 544.68 | 9 | 8 | 0 | 97.36 | 5.24 | − 7.13 | 0.0225 | 99.30 | 40.17 | 94.56 | 0.06 |
T6 | 488.61 | 6 | 7 | 0 | 80.29 | 4.90 | − 6.53 | 0.0005 | 99.12 | 46.47 | 96.20 | 0.06 |
T7 | 502.64 | 7 | 7 | 0 | 80.29 | 5.36 | − 6.84 | 0.0775 | 99.12 | 49.14 | 98.43 | 0.09 |
Control-ligands | ||||||||||||
ANK | 509.55 | 10 | 9 | 3 | 176.34 | 1.83 | − 3.37 | 0.0004 | 46.52 | 17.57 | 87.45 | 0.04 |
AZT | 748.996 | 7 | 13 | 5 | 182.48 | 2.45 | − 3.33 | 0.0004 | 69.32 | 31.40 | 14.49 | 0.06 |
BRT | 371.42 | 4 | 6 | 1 | 120.56 | 0.40 | − 0.14 | 0.7179 | 93.54 | 3.08 | 78.87 | 0.00 |
CLQ | 319.88 | 8 | 3 | 1 | 30.61 | 4.53 | − 4.59 | 0.0095 | 98.05 | 56.61 | 92.53 | 7.73 |
RDS | 602.585 | 14 | 9 | 4 | 203.55 | 1.71 | − 3.18 | 0.0006 | 53.50 | 3.26 | 81.26 | 0.04 |