Synthesis and anti-cancer activity of 5,6,7-substituted 2-fluorophenyl-4-quinolone derivatives

• Main Authors: Meng-Tung Tsai, 蔡孟東
• Other Authors: 郭盛助
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/31891195394357855010

碩士 === 中國醫藥大學 === 藥物化學研究所碩士班 === 97 === In our continuing work aimed at the discovery and development of novel anticancer agents, 2-(2-fluorophenyl)-6,7-(methylenedioxy)-4-quinolone was identified as a promising anticancer drug candidate. Encouraged by the preliminary results, 2-(2-fluorophenyl)-6,7-(methylenedioxy)-4-quinolone was used as a lead compound, a series of 5,6-(methylenedioxy)-2-fluorophenyl-4-quinolones 8a-8c, 5,6-dimethoxyl-2-fluorophenyl-4-quinolones 14a-14c, 5,6-dihydroxyl-2-fluorophenyl-4-quinolones 15a-15c, 5-hydroxyl-6-methoxyl-2-fluorophenyl-4-quinolones 16a-16c, 7-hydroxyl-6-methoxyl-2-fluorophenyl-4-quinolones 23a-23c were synthesized. The newly synthesized 5,6,7-substituted 2-fluorophenyl-4-quinolone derivatives were evaluated for cytotoxicity against several human cancer cell lines. Preliminary results showed that 2-(2-fluorophenyl)-5-hydroxyl-6-methoxyl-4-quinolone (16a) and 2-(3-fluorophenyl)-5-hydroxyl-6-methoxyl-4-quinolone (16b) show significant cytotoxicity against HL-60 (leukemia), colon cancer (HCT116), hepatoma (Hep 3B) and non-small-cell lung cancer (H460) cell (IC50 between 0.11-0.039 μM). These compounds were selected as the new lead compounds for further structure modification.