Table 1.
Effects of compounds 5a-qand 1on CHOP-Luc reporter and β cell viability against (tunicamycin) Tm
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|---|---|---|---|---|---|
| CompoundID | R1 | R2 | R3 | Max Activity (%)a | EC50 (μM)b |
| 1c | 3-Cl,2-Me | - | 2,5-di Me | 97 | 6 ± 1 |
| 5a | 3-Cl,2-Me | H | 2,5-di Me | 45 | 18 ± 4 |
| 5b | 3-Cl,2-Me | H | 2-Pyridine | 16 | 38 ± 9 |
| 5c | 3-Cl,2-Me | H | Indazole | Cytotoxic | - |
| 5d | 3-Cl,2-Me | H | 4-OMe | 55 | 32 ± 7 |
| 5e | 3-Cl,2-Me | H | 4-SO2NH2 | 52 | 40 ± 12 |
| 5f | 3-Cl,2-Me | H | Tyramine | 41 | 34 ± 8 |
| 5g | 3-Cl,2-Me | H | 4-CF3 | 88 | 13 ± 1 |
| 5h | 3-Cl,2-Me | H | 3-OMe,4-OH | 100 | 10 ± 2 |
| 5i | 3-Cl,2-Me | H | 3-CF3 | 46 | 32 ± 7 |
| 5j | H | H | 4-CF3 | 35 | 43 ± 11 |
| 5k | 4-Et | H | 4-CF3 | 42 | 45 ± 8 |
| 5l | 4-F | H | 4-CF3 | 12 | 41 ± 6 |
| 5m (WO5m) | 3-OH | H | 4-CF3 | 100 | 0.1 ± 0.01 |
| 5n | 3-OH | H | 3-OMe,4-OH | 30 | 65 ± 8 |
| 5o | 3-OMe,4-OH | H | 4-CF3 | 43 | 29 ± 6 |
| 5p | 3-Cl,2-Me | Me | 4-CF3 | 34 | 63 ± 4 |
| 5q | 3-Cl,2-Me | Tyrosine | 4-CF3 | Cytotoxic | - |
Maximum activity value is reported as % rescue from Tm (0.15 μg/mL) -induced reduction of cell viability, as measured by intracellular ATP levels; the values for Tm treatment alone and control (DMSO, without Tm) treatment are designated as 0% and 100%, respectively.
EC50 values (the concentrations that reach half-maximal activity) for INS-1 cell viability are calculated with GraphPad Prism from the data of ten 2-fold serial titration points in all tables. All experiments were performed in triplicate.
Compound 1 contains the 1,2,3-triazole group, as shown in Figure 1.
