Microwave-Assisted Synthesis of 1-Arylpyrrolo[3,2-c]quinolin-4-one Derivatives as Potential Anticancer Agents

• Main Authors: Da Wei, 簡大為
• Other Authors: Grece Chen
• Format: Others
• Language: zh-TW
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/01816104057570162181

碩士 === 靜宜大學 === 應用化學研究所 === 99 === This thesis probes a one-pot reaction by microwave radiation for the synthesis of 1-arylpyrrolo[3,2-c]quinolin-4-one derivatives as anticancer agents. Combretastatin A-4 (CA-4) related derivatives possess potency on inhibition of tubulin polymerization, and they are known to have a bridge skeleton to fix two aryl rings with methoxy groups in cis conformation. Therefore, a series of 1-arylpyrrolo[3,2-c]quinolin-4-one derivatives were designed. First, one-pot reaction by the use of microwave radiation afforded symmetric product 2-(2-ethoxyethyl)-N,N-diaryl malonamide (2), which was then followed by intramolecular cyclization reaction to provide the key intermediates 1-aryl-2,3-dihydro-1H-pyrrolo[3,2-c]quinolin-4-one 3a-n. Finally, the planar 1-arylpyrrolo[3,2-c]quinolin-4-one derivatives 4a-n were obtained by dehydrogenation reaction with the use of Pd/C in diphenyl ether at reflux. The synthesized target compounds 4a-n were evaluated for in vitro cytotoxicity by SRB methods against gastric cancer cell lines AGS, lung cancer cell lines A549, and colon cancer cell lines HT-29. Compounds 4a-n exhibit selectivity on HT-29 cell lines. Further, more substituents on the aromatic ring in 4a-n result in better inhibitory activity. Among them, compound 4f shows 79% inhibition at the concentration of 1 M against HT-29 cancer cell lines.