Table 2.
In vitro inhibitory activity evaluation of identified top 35 Asinex hit compounds on human rChAT, rAChE and plasma BuChE.
| Compounds ID | ChAT | AChE | BuChE | ||||||
|---|---|---|---|---|---|---|---|---|---|
| % IRa | IC50 c (µM) | Kid (µM) | % IRb | IC50 c (µM) | Kid (µM) | % IRb | IC50 c (µM) | Kid (µM) | |
| A1 | 0.0 | — | — | 0.0 | — | — | 4.8 | — | — |
| A2 | 6.9 | — | — | 0.0 | — | — | 60.5 | 526.9 | 84.9 |
| A3 | 6.9 | — | — | 0.0 | — | — | 15.1 | — | — |
| A4 | 26.7 | — | — | 0.0 | — | — | 14.4 | — | — |
| A5 | 2.1 | — | — | 7.0 | — | — | 9.2 | — | — |
| A6 | 0.0 | — | — | 11.9 | — | — | 20.2 | — | — |
| A7 | 7.2 | — | — | 15.8 | — | — | 29.9 | — | — |
| B1 | 84.3 | 7.0 | 9.4 | 9.1 | — | — | 14.8 | — | — |
| B2 | 0.0 | — | — | 0.0 | — | — | 18.5 | — | — |
| B3 | 0.0 | — | — | 0.0 | — | — | 16.6 | — | — |
| B4 | 70.8 | 16.5 | 11.9 | 0.0 | — | — | 22.1 | — | — |
| B5 | 0.0 | — | — | 26.1 | — | — | 39.5 | — | — |
| B6 | 7.6 | — | — | 2.6 | — | — | 11.0 | — | — |
| B7 | 13.3 | — | — | 73.6 | 40.1 | 65.4 | 14.9 | — | — |
| C1 | 0.0 | — | — | 79.5 | 71.9 | 42.3 | 9.8 | — | — |
| C2 | 0.0 | — | — | 0.0 | — | — | 78.5 | 364.5 | 59.6 |
| C3 | 0.0 | — | — | 22.0 | — | — | 20.1 | — | — |
| C4 | 0.0 | — | — | 4.9 | — | — | 54.2 | 527.5 | 59.4 |
| C5 | 0.0 | — | — | 81.3 | 6.3 | 23.7 | 51.8 | — | — |
| C6 | nde | — | — | 33.1 | — | — | 34.7 | — | — |
| C7 | 0.0 | — | — | 15.7 | — | — | 29.4 | — | — |
| D1 | 0.0 | — | — | 0.0 | — | — | 20.0 | — | — |
| D2 | 0.0 | — | — | 18.1 | — | — | 7.0 | — | — |
| D3 | 0.0 | — | — | 53.2 | 250.8 | 177.1 | 20.7 | — | — |
| D4 | 3.5 | — | — | 74.8 | 145.9 | 141.1 | 18.2 | — | — |
| D5 | 0.0 | — | — | 4.2 | — | — | 7.8 | — | — |
| D6 | 4.8 | — | — | 0.0 | — | — | 9.3 | — | — |
| D7 | 0.0 | — | — | 27.7 | — | — | 22.4 | — | — |
| E1 | 55.2 | 25.4 | 15.2 | 12.4 | — | — | 17.2 | — | — |
| E2 | 4.1 | — | — | 2.7 | — | — | 12.0 | — | — |
| E3 | 10.3 | — | — | 10.2 | — | — | 23.0 | — | — |
| E4 | 4.8 | — | — | 1.5 | — | — | 11.7 | — | — |
| E5 | 0.0 | — | — | 4.1 | — | — | 12.8 | — | — |
| E6 | 2.5 | — | — | 0.0 | — | — | 13.2 | — | — |
| E7 | 0.0 | — | — | 0.5 | — | — | 37.5 | — | — |
| α-NETA | 93.7 | 0.1* | — | — | — | — | — | — | — |
a% Inhibition rate (IR) at a concentration of 100 µM for rChAT. b% IR at a concentration of 200 µM for rAChE and BuChE. % IR values are shows as mean of three individual experiments performed in triplicate. Results expressed as percentage inhibition compared to control. cThe half maximal inhibitory concentration (IC50) of the compounds to produce 50% inactivation of the enzymes; the values are shown as mean of two experiments. d The inhibitory constant (Ki) values indicate the potency of identified inhibitors; the values are shown as mean of two experiments. eCompound C6 interfered with ChAT fluorometric assay because of its colored nature. *As previously reported by our group 26. α-NETA = 2-(alpha-naphthoyl)ethyltrimethylammonium iodide; rChAT = recombinant choline acetyltransferase; rAChE = recombinant acetylcholinesterase.