Journal of Chinese Pharmaceutical Sciences ›› 2019, Vol. 28 ›› Issue (11): 786-801.DOI: 10.5246/jcps.2019.11.075

• Original articles • Previous Articles     Next Articles

Synthesis and biological evaluation of indeno[1, 2-b]indole derivatives as dual topoisomerase I & II inhibitors: novel multidrug resistant reversal anticancer agents

Dongbo Lu1, Yu Chen1, Shan Liu1, Chao Guo2, Xia Li2,3*, Zhongjun Li1, Xiangbao Meng1*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs; Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
    2. School of Ocean, Shandong University, Weihai 264209, China
    3. School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
  • Received:2019-05-27 Revised:2019-07-15 Online:2019-12-01 Published:2019-08-23
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  • Supported by:

    The National Natural Science Foundation of China (Grant No. 81573272, 81273370), Changjiang Scholars and Innovative Research Team in University (Grant No. IRT13028).


A single compound able to inhibit both Topo I and II may present the advantage of improving anti-proliferative activity, with reduced toxic side effects, with respect to the combination of two inhibitors. We designed and synthesized 28 compounds of indeno[1, 2-b]indole derivatives as a new class of Topo I and II inhibitor and successfully identified compound 2-3j, which showed the most potent cell growth inhibition with IC50 =0.74 μM against HCT-116 cell line. Compound 2-3j was also evaluated as a potent topoisomerase I and II inhibitor and can induce apoptosis in human colon cancer cells. 2-3j showed potency against a small panel of drug sensitive and multidrug resistant (MDR) cell lines, and it reversed the MDR of K562/A02, MCF-7/Adr, and KB/Vcr cells at 0.5 μM, with reversal fold values of 3.2, 10.1, and 5.8, respectively. 2-3j might inhibit the function of ABCG2 to increase intracellular drug accumulation and enhance the sensitivity of conventional chemotherapeutic agents for MDR cells. 2-3j could be a promising lead for the development of a new class of antitumor drug acting as inhibitors of Topo I & II and ABCG2.

Key words: Indeno[1, 2-b]indole, Anti-cancer, Topoisomerse I &, II inhibitor, Reverse multi-drug resistance

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