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Letters in Drug Design & Discovery

Author(s): Lifang Guo, Benshan Xu, Bin Hu*, He Liu* and Nan Song*

DOI: 10.2174/1570180819666220816114613

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Synthesis and Biological Evaluation of 4-substituted Aryl-piperazine Derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo [5.2.1.02,6] dec-8-ene-3,5-dione as Anti-cancer and Anti-angiogenesis Agents

Page: [1538 - 1543] Pages: 6

  • * (Excluding Mailing and Handling)

Abstract

Background: A series of aryl-piperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4- azatricyclo [5.2.1.02,6] dec-8-ene-3,5-dione were designed, synthesized, and their biological activities were evaluated.

Methods: The chemical structures of the desired compounds were identified by 1H NMR, ESI-MS and elementary analysis. The anti-cancer and anti-angiogenesis activities of the newly synthesized compounds were evaluated by proliferation and migration assays, respectively.

Results: The screening results demonstrated that compounds 2 and 5 showed potent anti-tumor activity (IC50 values ranging from 7.1 to 15.9μM) with low cytotoxic activities (IC50＞79.3μM). Although compound 5 had no effects on endothelial proliferation (IC50=65.3μM), it significantly abrogated endothelial cell migration (IC50=6.7μM).

Conclusion: This work may impart new direction for the investigations of aryl-piperazine derivatives and lead to the development of potent novel anti-tumor and anti-angiogenesis agents.

Keywords: 1, 7, 8, 9-tetrachloro-10, 10-dimethoxy-4-azatricyclo [5.2.1.02, 6] dec-8-ene-3, 5-dione, aryl-piperazine derivatives, anti-cancer activity, angiogenesis.

Graphical Abstract

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