Table 3.
Chemical structure, physicochemical descriptors, and the effect of the 4-aminoindole series of compounds on hIAPP and fIAPP aggregation measured as fluorescence intensity using ThT assay.
| ID# | Structure | MW | TPSA | cLogP | cLogD | LR5 | hIAPP | fIAPP |
|---|---|---|---|---|---|---|---|---|
| 17 |
|
269.2737 | 56.92 | 2.88 | 3.36 | Y | 22.5 ± 0.1 | 25.3 ± 1.9 |
| 18 |
|
319.2812 | 56.92 | 3.58 | 4.1 | Y | 14.0 ± 0.3 | 15.0 ± 2.1 |
| 19 |
|
319.2812 | 56.92 | 3.60 | 4.1 | Y | 16.7 ± 0.3 | 23.2 ± 0.9 |
| 20 |
|
296.2808 | 102.74 | 2.09 | 3.16 | Y | 26.9 ± 0.3 | 44.5 ± 1.9 |
| 21 |
|
299.7549 | 56.92 | 3.11 | 3.80 | Y | 31.1 ± 0.2 | 39.9 ± 0.9 |
| 22 |
|
265.3098 | 56.92 | 2.90 | 3.73 | Y | 22.6 ± 1.0 | 34.1 ± 2.8 |
| 23 |
|
281.3092 | 66.15 | 2.54 | 3.06 | Y | 11.6 ± 0.2 | 18.1 ± 0.6 |
| 24 |
|
311.3352 | 75.38 | 2.54 | 2.90 | Y | 7.5 ± 0.4 | 6.9 ± 1.4 |
Notes: TPSA, Log P, and Log D were obtained with SwissADME or Chemaxon. The ThT (%) represent the maximum fluorescence intensity obtained at the plateau phase of the kinetics of fibrillization using 10 µM of IAPP. Compounds were tested at 100 µM (molar ratio 1:10). ThT % indicated are average with SEM. These results are representative of three independent experiments performed with technical triplicates. cLogD: calculated distribution coefficient at 7.4; cLogP: calculated partition coefficient; LR5: Lipinski’s rule of five; MW: molecular weight; ThT: Thioflavin T; TPSA: topological polar surface area.