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. 2022 Nov 29;13(23):3314–3329. doi: 10.1021/acschemneuro.2c00357

Table 1. Inhibitory Activity of Bivalent Derivatives 124 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.
a

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.

b

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.