Synthesis and Biological Evaluation of 4-substituted Aryl-piperazine Derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4-azatricyclo [5.2.1.0^2,6] dec-8-ene-3,5-dione as Anti-cancer and Anti-angiogenesis Agents

Background: A series of aryl-piperazine derivatives of 1,7,8,9-tetrachloro-10,10-dimethoxy-4- azatricyclo [5.2.1.0^2,6] 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 (IC5079.3μM). 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.