Table 1.
50% Inhibitory Concentration of Compounds Versus Freshly Prepared Human Erythrocyte AChE and Plasma BChE, and computed Log D value
| No. | Compound | AChE | BChE | a Selectivity A/B or B/A | d Log D |
|---|---|---|---|---|---|
| (IC50, nM, ± SEM) | |||||
| 3 | Neostigmine methyl sulfate | 18.8±3.0 | 60±2 | 3.2 AChE | −2.09 |
| 4 | Pyridostigmine bromide | 360±30 | 900±100 | 2.5 AChE | −2.84 |
| 5 | N-Phenylcarbamate of 3-dimethylaminophenol | 2500±130 | 18,000±3000 | 7.2 AChE | 3.06 |
| 6 | N-Phenylcarbamate of 3-phenol-1-trimethyl ammonium methylsulfate | 1875±110 | 18,000±2200 | 9.6 AChE | −1.4 |
| 7 | N-Phenylcarbamate of 3-hydroxypyridine | >30,000b | >30,000b | None | 1.78 |
| 8 | N-Phenylcarbamate of 3-hydroxy-1-methyl pyridinium bromide | >30,000b | 550±200 | BChE | −2.21 |
| 9 | (−)-Physostigmine | 27.9±2.4 | 16.0±2.9 | 1.7 BChE | 0.42 |
| 10 | (−)-N(1)-Methylammonium bromide of physostigmine | 26.1± 6.2 | 130±15 | 5 AChE | −1.04 |
| 11 | (−)-Phenserine | 24.0±6.0 | 1560±60.0 | 65 AChE | 2.22 |
| 12 | (−)-N(1)-Methylammonium bromide of phenserine | 25.4±2.8 | 210±90 | 8.3 AChE | −0.5 |
| 13 | (−)-Tolserine | 10.3±1.6 | 1950±245 | 189 AChE | 2.66 |
| 14 | (−)-N(1)-Methylammonium bromide of tolserine | 14.6±1.2 | 140±60 | 9.6 AChE | −0.17 |
| 15 | (−)-Cymserine | 760±21 | 51±1.0 | 14.9 BChE | 3.51 |
| 16 | (−)-N(1)-Methylammonium bromide of cymserine | 145±14 | 43±23 | 3.4 BChE | 1.0 |
| 17 | (−)-Phenethylcymserine | >30,000b | 6.0±1.0 | >5000 | 5.72 |
| 18 | (−)-N(1)-Methylammonium bromide of phenethylcymserine | 300±22 | 51±2.6 | 5.9 BChE | 2.43 |
a
A/B or B/A: selectivity for AChE or BChE from IC50 values.
b
None: Insufficient activity in the range of 0.3 nM to 30 μM to calculate an IC50 value, and thus considered inactive.
c
The IC50 data of 9, 11, 13, 15 from ref. (Brzostowska et al., 1992)12, and 17 from ref. (Yu et al., 1999)21.
d
ACD/PhysChem Suite version 12.01 and PrologD (CompuDrug, Pallas).