Discovery of indeno[1,2-c ]quinoline derivatives as dual topoisomerases I/II inhibitors: Part 3

Chih Hua Tseng, Cherng Chyi Tzeng, Chiao Li Yang, Pei Jung Lu, Yu Peng Liu, Hui Ling Chen, Chien Yu Chen, Chia Ning Yang, Yeh Long Chen

研究成果: Article同行評審

14 引文 斯高帕斯(Scopus)


(E) -6-Hydroxy-9-methoxy-6-(piperazin-1-yl)-11 H -indeno[1,2-c ]quinolin-11-one O -2-(pyrrolidin-1-yl)ethyl oxime (2c) was identified as a potential dual topo I/II inhibitor in our previous paper. In continuation for the search of more potent compounds, we describe herein the preparation of certain indeno[1,2-c ]quinoline derivatives and evaluation of their antiproliferation, DNA binding affinity, and topoisomerases (topo I and topo II) inhibitory activities. Among them, (E) -9-[3-(dimethylamino)propoxy]-11 H -indeno[1,2-c ]quinolin-11-one O -3-(dimethylamino)propyl oxime (11b) and its analog 11c exhibited approximately equal activity to the lead compound 2c against the growth of HeLa and A549 cancer cells. Both compounds 11b and 11c were more active than 2c in the inhibition of topo I and topo II. However, none of them exhibited significant DNA binding affinity while 2c was a very strong DNA binding agent. Compound 11b exhibited a high oral bioavailability of 39.8 % while the oral bioavailability of 2c and 11c was only 10.9 and 8.6 %, respectively. The in vivo anti-tumor evaluation of 11b in nude mice bearing subcutaneous breast cancer tumors revealed that treatment with low (10 mg/kg) or high (30 mg/kg) doses of 11b dramatically diminished tumor growth. Therefore, compound 11b is identified as a potential non-DNA intercalating dual topo I/II inhibitor.

頁(從 - 到)781-799
期刊Molecular Diversity
出版狀態Published - 2013 十一月

All Science Journal Classification (ASJC) codes

  • 催化
  • 資訊系統
  • 分子生物學
  • 藥物發現
  • 物理與理論化學
  • 有機化學
  • 無機化學


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