Table 1.
Physicochemical parameters of Cinchona alkaloids. cpd. = compound, VAR = calculated vacuolar accumulation ratio. S = chloroquine-sensitive, R = chloroquine-resistant. S/R = ratio of IC50 values. BHIA = % inhibition in β-haematin inhibition test
| Cpd. | pKa1 | pKa2 | Log P | Log D (pH7.4) | Log D (pH5.2) | VAR | IC50 nM S | IC50 nM R | RATIO S/R | BHIA % inhib. |
| Q | 8.58a | 4.12b | 3.17c | 1.97e | 0.30 | 161.0 | 29.315 | 103.215 | 0.28 | 84 ± 1 |
| 2.79d | 1.96f | -0.25f | ||||||||
| QD | 8.58g | 4.42h | 2.84i | 1.66j | 0.40k | 173.2 | 13.415 | 43.715 | 0.31 | 85 ± 9 |
| 2.79d | 1.63f | -0.61f | ||||||||
| HQ | 9.01 l | 4.29 | 3.07 | 1.50 | 0.53 | 173.6 | 21.315 | 151.715 | 0.14 | 93 ± 0.6 |
| 3.27d | 1.45f | -0.79f | ||||||||
| HQD | 9.16 | 4.34 | 3.43 | 1.72 | 0.75 | 177.5 | 10.415 | 74.115 | 0.14 | 95 ± 0.4 |
| 3.27d | 1.66f | -0.59f | ||||||||
| C | 8.35m | 4.28n | 2.82o | 1.85p | -0.38f | 159.6 | 18.346 | 70.846 | 0.26 | 94 ± 0.5 |
| 2.49d | 1.82f | |||||||||
| CD | 8.40q | 4.17r | 2.68s | 1.73t | -0.56f | 157.5 | 69.546 | 206.846 | 0.34 | 94 ± 0.4 |
| 2.49d | 1.64f | |||||||||
| EQ | 9.54u | 4.08 | 2.90 | 0.76 | -1.44 | 169.2 | 347115 | 117915 | 2.94 | 2 ± 13 |
| 2.79d | 0.76f | -1.47f | ||||||||
| EQD | 9.39v | 4.15 | 2.53 | 0.55 | -1.2 | 170.8 | 270015 | 102415 | 2.64 | 12 ± 12 |
| 2.79d | 0.54f | -1.70f | ||||||||
| CQ | 10.18 | 8.38 | 4.72 | 0.96 | -3.44 | 22750 | 18.5 | 264 | 0.07 | 81 ± 15 |
| 0.92f | -3.44f | |||||||||
| VE | 8.462 | <0 | 3.7962 | 2.75f | 0.59f | 144.2 | 720053 | 250053 | 2.88 | 0 ± 21 |
| PMZ | 9.1142 | <0 | 4.7542 | 3.03f | 0.84f | 155.5 | 143652 | 83552 | 1.70 | 15 ± 22.5 |
a: Lit 8.43[64], 8.4[39], 8.05[65], 8.59[66]. In 80% methylcellosolve/20% water 7.73[41], 7.25[67] ; b: Lit. 4.34[64],4.32 [39], 4.33 [66]. In 80% methylcellosolve 2.81[67], 2.38[68] ; c: Lit. 3.44[22], 2.64[65] ; d: Calc. from CLogP ; e: Lit. 1.90[65], 2.14[22], 2.54[69], 1.73(pH7.0)[70] ; f: Calc from eqn. (1). ; g: Lit. 8.79[64], 7.95[41], 8.78[42]. In 80% methylcellosolve 7.95[41]7.36[67] ; h: Lit. 4.34[64], in 80% methylcellosolve 2.66[67], 2.40[68] ; i: Lit: 2.88[65], 3.71[42] ; j: Lit. 2.03[72], 2.07[74],2.11[31], 2.22[65]; k: Lit: -0.07[42] ; l: Lit. 8.87[40] ; m: Lit. 8.35[40], 8.32[65]. In 80% methylcellosolve 7.36[68] ; n: Lit. 4.28[67], In 80% methylcellosolve 2.80[67], 2.15[68] ; o: Lit 2.82[65]; p: Lit 1.85[65] ; q: Lit. 8.40[40], 8.30[65]; r: Lit. 4.17[40]. In 80% methylcellosolve 2.66[67], 2.12[68] ; s: Lit. 2.68[65] ; t: Lit. 1.73[65] ; u: Lit. In 80% methylcellosolve 8.44[41] ; v: Lit. in 80% methylcellosolve 8.32[41].