Table 1.
Cholinesterase inhibition, anti-BACE1, anti-MAO B and antioxidant capacity of 4-methylcoumarin and thiocoumarin derivatives
| Compounds | Structures | IC50 (µM) or % inhibition at 80 µM | Selectivity | Percentage inhibition for BACE 1 (*) | Percentage inhibition for MAO B (*) | Fe equivalent (µM ± SEM) (*) | Trolox equivalent (µM ± SEM) (*) | |
|---|---|---|---|---|---|---|---|---|
| AChE | BuChE | |||||||
| C1 | R1 = R2 = OH, R3 = R4 = R5 = H,R6 = O | n.a | 55.44 ± 5.30 | – | 19.35 ± 1.23% | n.d | 831.93 ± 17.81 | 393.35 ± 10.25 |
| C2 | R1 = R2 = OPr, R3 = R4 = R5 = H, R6 = O | 40.59 ± 0.95% | 35.78 ± 0.13% | – | n.a. | n.a. | – | – |
| C3 | R1 = R2 = OPr, R3 = R4 = R5 = H, R6 = S | 5.63 ± 1.68 | 17.02 ± 3.67 | 3.03 | 57.23 ± 1.76% | 31.99 ± 1.56 | 799.83 ± 9.13 | 357.36 ± 5.63 |
| C4 | R1 = R2 = OAc, R3 = R4 = R5 = H, R6 = O | 17.87 ± 2.37 | 38.93 ± 3.57 | 2.17 | 11.92 ± 0.78% | 25.62 ± 2.62 | 733.22 ± 15.98 | 364.92 ± 15.32 |
| C5 | R2 = OAc, R1 = R3 = R4 = R5 = H, R6 = O | 32.46 ± 1.35 | 10.23 ± 1.52% | – | n.a. | n.d. | – | – |
| C6 | R2 = R4 = OAc, R1 = R3 = R5 = H, R6 = O | 43.56 ± 2.32 | 92.85 ± 1.20 | 2.13 | 9.74 ± 0.89% | n.d. | – | – |
| C7 | R1 = R2 = OAc, R3 = R4 = R5 = H, R6 = S | 14.91 ± 2.29 | 3.40 ± 0.20 | 0.22 | 43.62 ± 0.95% | 17.06 ± 1.02 | 626.27 ± 5.42 | 260.52 ± 4.25 |
| C8 | R2 = R4 = OH, R1 = R3 = H, R5 = EtOAc, R6 = O | 41.99 ± 6.93 | > 100 | – | n.a. | n.a. | 249.31 ± 3.17 | 329.48 ± 7.35 |
| C9 | R1 = R2 = OBu, R3 = R4 = R5 = H, R6 = O | n.a | n.a | – | 20.06 ± 1.51% | n.d. | 126.33 ± 3.14 | 196.38 ± 1.23 |
| C10 | R2 = R3 = OAc, R1 = R4 = R5 = H, R6 = O | 29.49 ± 2.89 | > 100 | – | n.a. | n.d. | 518.28 ± 2.07 | 346.42 ± 2.36 |
| C11 | R1 = NHAc, R2 = OAc, R3 = R4 = R5 = H, R6 = O | 61.96 ± 5.62 | 98.54 ± 4.91 | – | 41.66 ± 1.36% | 12.05 ± 2.93 | – | – |
| C12 | R1 = R2 = OH, R4 = COOH, R3 = R5 = H, R6 = O | n.a | > 100 | – | 15.27 ± 0.76% | n.d. | 998.09 ± 12.66 | 421.59 ± 11.89 |
| C13 | R2 = OH, R3 = COOH, R1 = R4 = R5 = H, R6 = O | > 100 | 28.60 ± 1.25% | – | 30.65 ± 0.58% | 4.98 ± 0.89 | – | – |
| C14 | R2 = OAc, R3 = COOH, R1 = R4 = R5 = H, R6 = O | 79.43 ± 3.94 | n.a. | – | n.a. | n.d. | – | – |
| C15 | R2 = R5 = OH, R1 = R3 = R4 = H, R6 = O | n.a. | n.a. | – | 31.09 ± 1.83% | 12.91 ± 1.27 | 790.81 ± 36.41 | 311.46 ± 13.85 |
| Donepezil | 0.19 ± 0.02 | 5.75 ± 0.36 | – | – | – | |||
| Selegiline | – | – | – | 81.36 ± 0.38 | ||||
n.a. no activity was observed
n.d. activity was not determined
*All compounds were screened at 20 µM
aIC50, inhibitor concentration (mean ± SEM) resulting in 50% inhibition of the enzyme AChE
bIC50, inhibitor concentration (mean ± SEM) resulting in 50% inhibition of the enzyme BuChE
cSelectivity for AChE: (IC50 of BuChE)/(IC50 of AChE