Table 1. Inhibitory Activity of Bivalent Derivatives 1–24 toward Aβ42 and Tau Aggregation, Together with Neurotoxicity Data on Differentiated CGNs (24 h Treatment).
cmp | linker | R | % inhibition Aβ42 aggregation @ 10 μMa | % inhibition Tau aggregation @ 10 μMa | % survival neurotoxicity @ 10 μMb |
---|---|---|---|---|---|
1 | phenyl | -H | 25.4 ± 1.9 | 19.4 ± 3.6 | 77.6 ± 6.1 |
2 | biphenyl | -H | 20.2 ± 2.1 | 16.5 ± 3.1 | 81.3 ± 6.5 |
3 | diphenylmethane | -H | 12.9 ± 3.4 | 5.2 ± 2.7 | 62.4 ± 9.6 |
4 | carbazole | -H | 24.7 ± 4.1 | 21.2 ± 2.6 | 73.4 ± 5.1 |
5 | 9,9-dimethylfluorene | -H | 23.6 ± 2.6 | 14.8 ± 3.0 | 67.9 ± 5.4 |
6 | bisthiophene | -H | 42.4 ± 4.5 | 19.4 ± 3.9 | 89.9 ± 1.2 |
7 | phenyl | -CH2COOCH2CH3 | 40.7 ± 4.4 | 30.6 ± 3.6 | 90.1 ± 2.1 |
8 | biphenyl | -CH2COOCH2CH3 | 14.3 ± 3.5 | 18.1 ± 3.2 | 87.2 ± 3.1 |
9 | diphenylmethane | -CH2COOCH2CH3 | 14.5 ± 4.1 | 19.9 ± 3.6 | 88.7 ± 4.1 |
10 | carbazole | -CH2COOCH2CH3 | 31.9 ± 3.0 | 37.7 ± 4.1 | 84.2 ± 6.3 |
11 | 9,9-dimethylfluorene | -CH2COOCH2CH3 | 17.5 ± 4.5 | 33.1 ± 4.5 | 85.8 ± 6.9 |
12 | bisthiophene | -CH2COOCH2CH3 | 7.0 ± 3.7 | 9.2 ± 5.0 | 90.2 ± 2.1 |
13 | phenyl | -CH2COOH | 16.1 ± 3.9 | 25.3 ± 4.2 | 82.3 ± 2.9 |
14 | biphenyl | -CH2COOH | 35.1 ± 1.9 | 27.1 ± 2.5 | 89.0 ± 2.2 |
15 | diphenylmethane | -CH2COOH | 26.2 ± 1.9 | 3.8 ± 5.2 | 90.9 ± 1.5 |
16 | carbazole | -CH2COOH | 32.1 ± 3.1 | 37.9 ± 3.5 | 90.0 ± 2.8 |
17 | 9,9-dimethylfluorene | -CH2COOH | 51.4 ± 2.7 | 55.6 ± 3.2 | 89.3 ± 2.3 |
18 | bisthiophene | -CH2COOH | 65.6 ± 3.3 | 15.8 ± 4.7 | 90.9 ± 3.1 |
19 | phenyl | -CH2CH2N(CH3)2 | 8.1 ± 4.4 | 19.4 ± 3.6 | 89.4 ± 2.0 |
20 | biphenyl | -CH2CH2N(CH3)2 | 26.4 ± 4.2 | 34.9 ± 1.9 | 91.1 ± 0.9 |
21 | diphenylmethane | -CH2CH2N(CH3)2 | 16.1 ± 3.8 | 38.7 ± 3.3 | 91.1 ± 1.5 |
22 | carbazole | -CH2CH2N(CH3)2 | 74.0 ± 4.3 | 66.1 ± 3.9 | 94.3 ± 1.8 |
23 | 9,9-dimethylfluorene | -CH2CH2N(CH3)2 | 44.8 ± 4.7 | 41.9 ± 3.9 | 87.9 ± 3.4 |
24 | bisthiophene | -CH2CH2N(CH3)2 | 20.3 ± 4.8 | 17.3 ± 4.5 | 88.8 ± 2.3 |
Huprine Y | 4.6 ± 2.3 | n.d. | n.d. | ||
HUP7TH | 77.6 ± 1.5 | 69.5 ± 1.6 | n.d. | ||
Rhein | n.d. | 39.2 ± 2.1 | n.d. |
Inhibition of Aβ42 and Tau aggregation in intact E. coli cells upon treatment with a compound concentration of 10 μM. Values are expressed as the mean ± SEM of four independent experiments.
Viability of cerebellar granule neurons (CGNs) after 24 h of incubation with the test compound at a 10 μM concentration. The results are expressed as a percentage of healthy nuclei on the total nuclei counting number, after Hoechst staining, and are the mean ± SEM of three different experiments; n.d. not determined.