Synthesis, in vitro and in vivo anticancer activities of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine-3,5-dione derivatives

To develop potent and selective anticancer agents, a series of novel 4-substituted 1,2-bis(4-chlorophenyl)-pyrazolidine- 3,5-dione derivatives were designed and synthesized. All the compounds were evaluated for their antiproliferative activities against a panel of four human cancer cell lines. Among them, compound 4u is the most potent, exhibiting IC50 values ranging from 5.1 to 10.1 mu M. Flow cytometry and western blot analyses revealed that treatment of MGC-803 cells with compound 4u induces early cellular apoptosis via activation of caspases-9/3. Furthermore, compound 4u effectively reduced the tumor growth exhibited by human gastric cancer cells in vivo without obvious adverse side effects. Our findings indicate that compound 4u may serve as a lead compound to target solid tumors.