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
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 synthesized. The chemical structures of the desired compounds were identified by 1H NMR, ESI-MS and elementary analytical. 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 showed little effects on endothelia proliferation (IC50=65.3μM), it indeed significantly abrogated endothelia cell migration (IC50=6.7μM). Conclusions: 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.