Synthesis and Biological Evaluation of 4-Aroyl-6,7,8-Trimethoxyquinolines as a Novel Class of Anticancer Agents
Abstract
:1. Introduction
2. Results and Discussion
Cell Type ( IC50 ± SDa, nM) | |||||||||
---|---|---|---|---|---|---|---|---|---|
Compd | KB | HT29 | MKN45 | ||||||
7 | > 5,000 | > 5,000 | > 5,000 | ||||||
8 | > 5,000 | > 5,000 | > 5,000 | ||||||
9 | 1,297 | ± | 371 | 2,092 | ± | 281 | 1,436 | ± | 272 |
10 | 1,597 | ± | 94 | 1,725 | ± | 530 | 1,047 | ± | 87 |
11 | 217 | ± | 39 | 327 | ± | 93 | 239 | ± | 47 |
12 | > 5,000 | > 5,000 > 5,000 | > 5,000 | ||||||
> 5,000 | 14 | ||||||||
> 5,000 | > 5,000 | ||||||||
13 | > 5,000 | > 5,000 > 5,000 | > 5,000 | ||||||
> 5,000 | 15 | ||||||||
> 5,000 | > 5,000 | ||||||||
colchicine | 10.3 | ± | 0.9 | 16.2 | ± | 2.9 | 19.2 | ± | 1.0 |
Cell lines | Resistant type | IC50 ± SDa | |||
---|---|---|---|---|---|
Vincristine, nMb | Paclitaxel, nMb | VP-16, µMb | 11, nM | ||
KB | Parental | 0.4 ± 0.1 | 3.3 ± 1.2 | 1.1 ± 0.5 | 217.0 ± 39.0 |
KB-VIN10 | MDR ↑ | 90.1 ± 7.4 | 16500 ± 707 | 23 ± 3 | 245.6 ± 8.5 |
KB-S15 | MDR ↑ | 17.6 ± 2.2 | 273 ± 15 | 3.5 ± 0.3 | 213.3 ± 96.1 |
KB-7D | MRP ↑ | 1.2 ± 0.4 | 7.9 ± 0.5 | 54 ± 3.5 | 252.3 ± 15.0 |
Compd. | TubulinaIC50 ± SD (µM) | Colchicine bindingb (%) | |
---|---|---|---|
1 µM | 5 µM | ||
11 | >10 | 37.6 | 45.6 |
colchicine | 7.3 | 58.7 | 80.8 |
3. Experimental
3.1. General
3.2. Chemistry
3.2.1. General procedure for synthesis of compounds 7-11
3.3. Cell Growth Inhibitory Assay
3.4. Tubulin Polymerization in Vitro Assay [13,15]
3.5. Tubulin Competition-Binding Scintillation Proximity Assay [17,18,19]
4. Conclusions
Acknowledgements
References
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Hsieh, C.-C.; Lee, H.-Y.; Nien, C.-Y.; Kuo, C.-C.; Chang, C.-Y.; Chang, J.-Y.; Liou, J.-P. Synthesis and Biological Evaluation of 4-Aroyl-6,7,8-Trimethoxyquinolines as a Novel Class of Anticancer Agents. Molecules 2011, 16, 2274-2284. https://doi.org/10.3390/molecules16032274
Hsieh C-C, Lee H-Y, Nien C-Y, Kuo C-C, Chang C-Y, Chang J-Y, Liou J-P. Synthesis and Biological Evaluation of 4-Aroyl-6,7,8-Trimethoxyquinolines as a Novel Class of Anticancer Agents. Molecules. 2011; 16(3):2274-2284. https://doi.org/10.3390/molecules16032274
Chicago/Turabian StyleHsieh, Cheng-Chih, Hsueh-Yun Lee, Chih-Ying Nien, Ching-Chuan Kuo, Chi-Yen Chang, Jang-Yang Chang, and Jing-Ping Liou. 2011. "Synthesis and Biological Evaluation of 4-Aroyl-6,7,8-Trimethoxyquinolines as a Novel Class of Anticancer Agents" Molecules 16, no. 3: 2274-2284. https://doi.org/10.3390/molecules16032274