| 摘要: | 在我們不斷的探索及開發新穎抗癌藥的歷程中，2-(3-fluorophenyl)-6-methoxy-4-quinolone-3-carboxylic acid被發現為具有良好抗癌活性的候選藥物。
由於此項初步成果，因而以2-(3-fluorophenyl)-6-methoxy-4-quinolone-3-carboxylic acid為先導化合物，合成一系列2-(2,3- substituted phenyl)-6,7-substituted 4-quinolone-3-methanols (42–55)、2-(2,3-substituted phenyl)-6,7-substituted 4-quinolone-3-carbaldehydes (56–58)、2-(2,3-substituted phenyl)-6,7-substituted 4-quinolone-3-oximes (59–64)、及2-(2,3-substituted phenyl)-N-substituted-6,7-substituted 4- quinolone-carboxamides (65–94)的化合物。
檢視標的化合物的42–94 的細胞致毒活性及aurora A kinase 抑制活性。初步結果顯示化合物3-((2-Hydroxyethylimino)methyl) -6-methoxy-2-phenyl-4-quinolone (61)以及3-((2-Hydroxyethylimino) methyl)-6,7-methylenedioxy-2-phenyl-4-quinolone (62)具有明顯的aurora A kinase抑制活性，二者值得更深入的探討。
In our continuing work aimed at the discovery and development of novel anticancer agents, 2-(3-fluorophenyl)-6-methoxy-4-quinolone-3- carboxylic acid was identified as a promising anticancer drug candidate.
Encouraged by the preliminary results, 2-(3-fluorophenyl)-6- methoxy-4-quinolone-3-carboxylic acid was used as a lead compound, a series of 2-(2,3-substituted phenyl)-6,7-substituted 4-quinolone-3- methanols (42 – 55), 2-(2,3-substituted phenyl)-6,7-substituted 4-quinolone-3-carbaldehydes (56–58), 2-(2,3-substituted phenyl)-6, 7-substituted 4-quinolone-3-oximes (59–64), and 2-(2,3-substituted phenyl) -N-substituted-6, 7-substituted 4-quinolone-carboxamides (65–94) were synthesized.
The target compound 42–94 were examined for their cytotoxicity and inhibitory effect on aurora A kinase activity. Preliminary results showed that 3-((2-hydroxyethylimino)methyl)-6-methoxy-2-phenyl-4-
quinolone (61) and 3-((2-hydroxyethylimino)methyl)-6,7-methylenedioxy
-2-phenyl-4-quinolone (62) exhibited significant effect on aurora A kinase. These two compounds are worthy for further exploration. |
