2. Academic Validation
  3. Antiproliferative and apoptosis-inducing activities of novel naphthalimide-cyclam conjugates through dual topoisomerase (topo) I/II inhibition

Antiproliferative and apoptosis-inducing activities of novel naphthalimide-cyclam conjugates through dual topoisomerase (topo) I/II inhibition

  • Bioorg Med Chem. 2015 Sep 1;23(17):5672-80. doi: 10.1016/j.bmc.2015.07.011.
Shaoying Tan 1,  Deheng Sun 1,  Jiankun Lyu 1,  Xiao Sun 1,  Fangshu Wu 1,  Qiang Li 1,  Yiqi Yang 1,  Jianxu Liu 1,  Xin Wang 1,  Zhuo Chen 2,  Honglin Li 3,  Xuhong Qian 1,  Yufang Xu 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
  • 2 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: chenzhuo@ecust.edu.cn.
  • 3 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: hlli@ecust.edu.cn.
  • 4 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: yfxu@ecust.edu.cn.
PMID: 26211460 DOI: 10.1016/j.bmc.2015.07.011
Abstract

A novel series of naphthalimide-cyclam conjugates were designed and synthesized. Among them, compounds 4c, 4d, 8c and 8d which bearing long lipophilic alkyl chains, displayed comparable or more potent cytotoxic activities against human tumor cell lines than amonafide. Furthermore, the four compounds were proved to possess strong inhibition against both Topoisomerase I and II. The representative compound 8c exhibited moderate DNA intercalation activity. Molecular modeling studies identified the possible interaction of compound 8c with the molecular target by forming Topoisomerase/DNA/drug ternary complex. Finally, derivatives with long lipophilic alkyl chains could efficiently induce Apoptosis.

Keywords

Antitumor agents; Apoptosis; DNA intercalation; Naphthalimide–cyclam conjugates; Topoisomerase I; Topoisomerase II.

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