Three-component synthesis and anticancer evaluation of pyrano[3,2-c]quinolones 6.
| ||||
|---|---|---|---|---|
| Compound | R | Yield 6 (%) | GI50b (μM) | |
| HeLa | MCF-7 | |||
| 6a | C6H5 | 78 | 0.39 ± 0.01 | 3.38 ± 0.53 |
| 6b | 3,4,5-(MeO)3C6H2 | 86 | 0.24 ± 0.02 | 1.0 ± 0.3 |
| 6c | 3-OH-4-MeOC6H3 | 82 | >50 | >50 |
| 6d | 3-MeO-4-OHC6H3 | 84 | 0.63 ± 0.05 | 0.5 ± 0.14 |
| 6e | 3-MeO-4-OH-5-NO2C6H2 | 89 | 0.63 ± 0.02 | 0.71 ± 0.12 |
| 6f | 3-NO2C6H4 | 77 | 0.32 ± 0.02 | 1.1 ± 0.1 |
| 6g | 2-NO2C6H4 | 73 | 5.0 ± 1.4 | 3.5 ± 0.3 |
| 6h | 4-Pyridinyl | 79 | >50 | 32 ± 2 |
| 6i | 3-Pyridinyl | 81 | 2.0 ± 0.1 | >50 |
| 6j | 2-Furanyl | 75 | 22 ± 1 | 35 ± 2 |
| 6k | 5-Methyl-2-furanyl | 78 | 3.9 ± 0.2 | 5.1 ± 0.1 |
| 6l | 2,3-(Cl)2C6H3 | 95 | 1.8 ± 0.2 | >50 |
| 6m | 2,6-(Cl)2C6H3 | 88 | >50 | 36 ± 2 |
| 6n | 3,4-(Cl)2C6H3 | 97 | 0.3 ± 0.03 | 2.5 ± 0.3 |
| 6o | 3-ClC6H4 | 91 | 0.15 ± 0.04 | 2.2 ± 0.2 |
| 6p | 3-FC6H4 | 90 | 0.30 ± 0.01 | 1.0 ± 0.3 |
| 6q | 3-BrC6H4 | 93 | 0.74 ± 0.03 | 0.003 ± 0.001 |
| 6r | 3-Br-4-FC6H3 | 95 | 0.27 ± 0.03 | 0.81 ± 0.08 |
| 6s | 3,5-(Br)2-4-OHC6H2 | 92 | 0.27 ± 0.02 | 0.43 ± 0.01 |
| 6t | 3-Br-4-OH-5-MeOC6H2 | 94 | 0.047 ± 0.01 | 0.39 ± 0.16 |
| 6u | 3-Br-4,5-(MeO)2C6H2 | 95 | 0.014 ± 0.003 | 0.38 ± 0.03 |
| 6v | 3,5-(Br)2C6H3 | 82 | 0.077 ± 0.006 | 0.075 ± 0.007 |
| 6w | 3-Br-4-MeOC6H3 | 64 | 0.41 ± 0.04 | 0.5 ± 0.1 |
| 6x | 5-Bromopyridin-3-yl | 85 | 0.013 ± 0.003 | 0.015 ± 0.008 |
| 6y | 3-Br-4-AcO-5-MeOC6H2 | 84 | 0.18 ± 0.02 | 0.025 ± 0.06 |
a
Reaction conditions: aldehyde 1 (0.8 mmol), malononitrile 2 (0.8 mmol), 4-hydroxy-1-methylquinolin-2(1H)-one 5 (0.8 mmol), triethylamine (45 mol%), EtOH (3 mL), reflux, 50 min.
b
Compound concentration required to reduce HeLa and MCF-7 cells viability by 50% after 48 h treatment relative to 100% DMSO control as assessed with the MTT assay. Data shown are average ± SD of two independent experiments.