Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones

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• 作者：Hee-Kyung Rhee ; Hyen Joo Park ; Sang Kook Lee ; Chong-Ock Lee ; Hea-Young Park Choo
• 关键词：Benzofuroquinolinediones ; Human cancer cell lines ; Cytotoxicity ; Topoisomerase II
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2007
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 February 2007
• 卷：15
• 期：4
• 页码：1651-1658
• 文件大小：343 K

摘要

Benzofuroquinolinediones (7c and 7d) were synthesized by base-catalyzed condensation of dichloroquinolinediones with phenolic derivatives. Their dialkylaminoalkoxy derivatives (8i–8p) were prepared by reaction with various dialkylaminoalkyl chlorides. The cytotoxicity of the synthesized compounds was evaluated against eight types of human cancer cell lines, and their topoisomerase II inhibition was assessed. In general, the cytotoxicity of benzofuroquinolinediones (8i–8p) was similar or superior to that of doxorubicin and showed more potent inhibitory activity than naphthofurandiones (8a–8h). Also, most of the compounds exhibited excellent topoisomerase II inhibitory activity at a concentration of 5 μM and two compounds, 8d and 8i, showed IC₅₀ values of 1.19 and 0.68 μM, respectively, and were much more potent than etoposide (IC₅₀ = 78.4 μM), but similar to doxorubicin (IC₅₀ = 2.67 μM). However their inhibitory activity on topoisomerase I was lower, and 8d and 8i showed IC₅₀ values of 42.0 and 64.3 μM, respectively.