Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones
Synthesis, cytotoxicity, and DNA topoisomerase II inhibitory activity of benzofuroquinolinediones
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DOI：
10.1016/j.bmc.2006.12.012
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发表时间：
2007-02-15
影响因子：
3.5
通讯作者：
Choo, Hea-Young Park
中科院分区：
文献类型：
--
作者：
Rhee, Hee-Kyung;Park, Hyen Joo;Choo, Hea-Young Park
以二氯喹啉二酮和酚类衍生物为原料，在碱催化下缩合合成了苯并呋喃并喹啉二酮（7 c和7 d）。它们的二烷基氨基烷氧基衍生物（8i-8 p）是通过与各种二烷基氨基烷基氯化物反应制备的。对8种类型的人类癌细胞系的细胞毒性的合成的化合物进行了评价，并评估其拓扑异构酶II抑制。一般而言，苯并呋喃并喹啉二酮（8i-8 p）的细胞毒性与阿霉素相似或上级，并且显示出比萘并呋喃二酮（8a-8h）更强的抑制活性。此外，大多数化合物在5 μ M浓度下显示出优异的拓扑异构酶II抑制活性，两种化合物8d和8i在5 μ M浓度下显示出抑制活性的IC 50值，两种化合物8d和8i分别显示出1.19和0.68 μ M的IC 50值，并且比依托泊苷（IC 50 = 78.4 μ M）有效得多，但与多柔比星（IC 50 = 2.67 μ M）相似。但它们对拓扑异构酶I的抑制活性较低，8d和8i的IC_（50）值分别为42.0和64.3 μ M。(c)2007爱思唯尔有限公司保留所有权利。
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 mu M and two compounds, 8d and 8i, showed IC50 values of inhibitory activity at a concentration of 5 mu M and two compounds, 8d and 8i, showed IC50 values of 1.19 and 0.68 mu M, respectively, and were much more potent than etoposide (IC50 = 78.4 mu M), but similar to doxorubicin (IC50 = 2.67 mu M). However their inhibitory activity on topoisomerase I was lower, and 8d and 8i showed IC50 values of 42.0 and 64.3 mu M, respectively. (c) 2007 Elsevier Ltd. All rights reserved.